Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Open accessAbstract
The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation of the lung, fibrosis, and lung cancer. How the presence of pathogenic dust is recognized and how chronic inflammatory diseases are triggered are poorly understood. Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1β secretion. Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis. (NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate.) In a model of asbestos inhalation, Nalp3 –/– mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production. Our findings implicate the Nalp3 inflammasome in particulate matter–related pulmonary diseases and support its role as a major proinflammatory “danger” receptor.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 35 cited sources checked · 0 supported · 0 flagged
- Findingown data
Adding 130 mM KCl to THP1 cultures prevented IL-1β production triggered by asbestos.
“We inhibited K + efflux by adding high concentrations (130 mM) of KCl to the culture media of THP1 cells and found that asbestos-induced IL-1β production was blocked (Fig. 3A).”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
- Findingcitation
IL-1β production was independent of the Ipaf inflammasome.
“By contrast, IL-1β production was independent of the Ipaf inflammasome, which has been shown to activate caspase-1 and produce IL-1β in response to flagellin from Salmonella typhimurium and Legionella pneumophila (fig.S4) (11,12).”
Quote in the paperSubstantial claim0 of 2 sources checked - Findingown data
In primary human monocyte-derived macrophages, DEP did not cause IL-1β release.
“Primary human monocyte-derived macrophages also produced mature IL-1β after stimulation with asbestos or silica (Fig. 1C), while DEP exposure again did not result in IL-1β secretion.”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Treatment with NAC or APDC reduced IL-1β release triggered by asbestos, MSU, and ATP.
“IL-1β production was indeed impaired in response to asbestos, MSU and ATP when using these inhibitors (Fig. 3D), suggesting that ROS production was a necessary step in inflammasome activation.”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
- Findingown data
After asbestos exposure, Nalp3-deficient mice recruited markedly fewer cells to their lungs.
“However, significantly fewer cells were recruited to the lungs of Nalp3 -/- mice after exposure to asbestos (Fig. 4A).”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
- Findingown data
In Nalp3-/- mice exposed to asbestos, KC and IL-1β levels were lower.
“KC, a potent neutrophil chemoattractant, and IL-1β were decreased in Nalp3 -/-mice, whereas IL-12(p40) production was independent of Nalp3.”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
- Findingown data
Particulates activate caspase-1 in THP1 cells, producing the p10 fragment.
“To clarify this, we determined whether the particulates activate caspase-1 in THP1 cells and indeed found processing of caspase-1 into the p10 fragment (fig.S1).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Stimulation with asbestos or silica caused THP1 macrophage-like cells to release mature IL-1β.
“We indeed observed that the macrophage-like cell line THP1 secreted mature IL-1β upon stimulation with asbestos or silica (Fig. 1A).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Knockdown of p22phox highly diminished IL-1β secretion.
“To further corroborate NADPH oxidase as a source of ROS production, we knocked down the common NADPH oxidase subunit p22phox and found highly diminished IL-1β secretion (Fig. 3F).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Treating cells with latrunculin A produced the same result as cytochalasin D.
“The same effect was achieved by treating the cells with the inhibitor of actin polymerisation, latrunculin A (fig.S5).”
Quote in the paperNot a substantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
- Findingown data
Asbestos-induced IL-1β release and caspase-1 activation did not require TLR or IL-1 receptor signaling, because reducing or removing MyD88 had little or no effect.
“In contrast, Toll-like receptors (TLRs) or IL-1 receptors do not seem to be essential for asbestos signalling, since the knock-down or knock-out of MyD88, an intracellular adaptor protein mediating TLR and IL-1 receptor signalling, had no or little effects on IL-1β secretion and caspase-1 activation (Fig. 2A and fig.S3).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
DEP or CSE did not produce detectable IL-1β in THP1 cells after 6 h.
“In contrast, the addition of diesel exhaust particles (DEP) or cigarette smoke extract (CSE) did not result in the production of detectable IL-1β when measured after 6 h of exposure (Fig. 1A).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
IL-12(p40) production was independent of Nalp3.
“KC, a potent neutrophil chemoattractant, and IL-1β were decreased in Nalp3 -/-mice, whereas IL-12(p40) production was independent of Nalp3.”
Quote in the paperNot a substantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
- Findingown data
The amount of mature IL-1β released after asbestos exposure was similar to that seen with MSU.
“The secretion of mature IL-1β induced by asbestos was comparable to amounts observed with monosodium urate crystals (MSU), a known potent activator of IL-1β processing (7) (Fig. 1, A and B).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
Not checked in the free run.
- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Asbestos led to ROS generation under experimental conditions.
“In order to test this hypothesis, we investigated whether asbestos led to ROS generation under our experimental conditions, which was the case (fig.S6).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Nalp3-/- mice showed a significant rise in the count of mucin-producing distal bronchioles.
“Although mucin production, which parallels inflammatory changes in lungs and may occur to facilitate clearance of asbestos fibers (21), was similarly increased by asbestos in Nalp3 -/-and Nalp3 +/+ lungs, significant increases in the number of mucinproducing distal bronchioles, sites of impact of chrysotile asbestos fibers after inhalation, occurred in Nalp3 -/-mice (table S1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] source
Not checked in the free run.
- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
- Findingcitation
Mice exposed to asbestos had higher total cell counts in BALF than air-exposed controls.
“As previously shown (19,20), asbestos-exposed mice exhibited increased total cell numbers in bronchoalveolar lavage fluid (BALF) compared to air-exposed mice.”
Quote in the paperNot a substantial claim0 of 2 sources checked- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Findingown data
IL-1β release triggered by the non-crystalline Nalp3 activators R837 and nigericin was unchanged by cytochalasin D.
“Cytochalasin D inhibited not only secretion of mature IL-1β by asbestos (Fig. 3C), but also by the particulate MSU, while for non-crystalline Nalp3 activators such as R837 and nigericin, IL-1β secretion was not affected (Fig. 3C).”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
- Findingown data
Human monocyte-derived macrophages from primary cultures released mature IL-1β when exposed to asbestos or silica.
“Primary human monocyte-derived macrophages also produced mature IL-1β after stimulation with asbestos or silica (Fig. 1C), while DEP exposure again did not result in IL-1β secretion.”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Asbestos increased mucin production to a similar extent in lungs of both Nalp3-/- and Nalp3+/+ mice.
“Although mucin production, which parallels inflammatory changes in lungs and may occur to facilitate clearance of asbestos fibers (21), was similarly increased by asbestos in Nalp3 -/-and Nalp3 +/+ lungs, significant increases in the number of mucinproducing distal bronchioles, sites of impact of chrysotile asbestos fibers after inhalation, occurred in Nalp3 -/-mice (table S1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] source
Not checked in the free run.
- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
- Findingown data
Reducing Nalp3, ASC, or caspase-1 levels strongly decreased mature IL-1β release from THP1 cells, as seen with MSU or nigericin.
“Highly reduced secretion of mature IL-1β in Nalp3-, ASC-and caspase-1-knocked-down cells was observed, similar to patterns observed with MSU or the bacterial toxin nigericin (Fig. 2A).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Inert polystyrene beads did not activate IL-1β maturation.
“Inert particles, such as polystyrene beads, did not activate IL-1β maturation (Fig. 1B).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Reducing thioredoxin levels led to greater IL-1β release after asbestos or MSU exposure.
“Indeed, when asbestos and MSU were added to macrophages in which TRX was downregulated by shRNA, increased IL-1β secretion was observed (Fig. 3G).”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Findingown data
Asbestos exposure raised levels of multiple cytokines, among them IL-1β, KC, and IL-12(p40).
“Several cytokines were induced by asbestos, such as IL-1β, KC, and IL-12(p40) (Fig. 4C).”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Findingown data
Cytochalasin D blocked mature IL-1β release caused by asbestos and by MSU.
“Cytochalasin D inhibited not only secretion of mature IL-1β by asbestos (Fig. 3C), but also by the particulate MSU, while for non-crystalline Nalp3 activators such as R837 and nigericin, IL-1β secretion was not affected (Fig. 3C).”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
- Findingown data
In asbestos-exposed Nalp3-/- mice, infiltration by lymphocytes, eosinophils, and neutrophils was lower.
“Notably, lymphocyte, eosinophil and neutrophil infiltration was reduced in Nalp3 -/-asbestos-exposed mice (Fig. 4B).”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
- Premisecitation
The amount of ROS produced tracks with how toxic and pathogenic different asbestos varieties are.
“The generation of ROS correlates with toxicity and pathogenicity of different types of asbestos.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] source
Not checked in the free run.
- Premisecitation
Lowering intracellular K+ through efflux is required for Nalp3 activation by every known activator, including MSU.
“In favour of the latter assumption is the recent finding that potassium (K + ) efflux, lowering intracellular K + levels, is a requirement for Nalp3 inflammasome activation triggered by all known activators including MSU (13)(14)(15).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Anakinra, an IL-1 receptor antagonist, is used effectively to treat autoinflammatory syndromes and gout in patients.
“Since Anakinra (IL-1ra) is efficiently used in the clinical treatment of autoinflammatory syndromes (26) as well as gout patients (27), the present study suggests a potential use of Anakinra in order to slow down progression of asbestosis, silicosis and possibly other inflammatory lung diseases.”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
Reactive oxygen species, produced by a NADPH oxidase after particles are phagocytosed, trigger inflammasome activation by these particulates.
“Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis (NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate).”
Quote in the paperSubstantial claim - Premisecitation
Caspase-1, activated inside the inflammasome, cleaves proIL-1β to yield mature IL-1β.
“Mature IL-1β is produced by cleavage of the inactive proIL-1β precursor by caspase-1, which is activated within a large multi-protein complex, termed the inflammasome (8).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] source
Not checked in the free run.
- Interpretationown data
Inflammasome activation requires ROS production.
“IL-1β production was indeed impaired in response to asbestos, MSU and ATP when using these inhibitors (Fig. 3D), suggesting that ROS production was a necessary step in inflammasome activation.”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
- Interpretationown data
The results favor a model where NADPH oxidase-derived ROS participate in activating the Nalp3 inflammasome.
“Rather, our data support a model in which ROS generated by a NADPH oxidase are implicated in Nalp3 inflammasome activation (Fig. 4D).”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Interpretationown data
The remaining IL-1β release in knockdown cells probably reflects incomplete suppression of the targeted proteins.
“The residual IL-1β secretion observed in these cells is most likely due to incomplete shutdown of the corresponding proteins (fig.S2).”
Quote in the paperNot a substantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
- Premisecitation
In mice with bleomycin- or silica-induced lung fibrosis, giving IL-1 receptor antagonist lowered the fraction of damaged lung.
“Moreover, in a mouse model of bleomycin-or silica-induced pulmonary fibrosis, treatment with IL-1 receptor antagonist (IL-1ra) reduces the proportion of damaged lung (25).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] source
Not checked in the free run.
- Interpretationreasoning
The Nalp3 inflammasome probably does not recognize each particle through a distinct specific interaction.
“It seems unlikely, however, that each of the particles is”
Quote in the paperSubstantial claim - Premisecitation
Inflammation is a defining feature of asbestos or silica exposure, seen in animal models and in patients with asbestos-related lung disease.
“Inflammation is a hallmark of exposure to asbestos or silica and is observed both in animal models and in the lungs of patients with asbestos-related lung disease (1,3).”
Quote in the paperSubstantial claim0 of 2 sources checked
- May combine two claims. 17
- Classified as probably not a substantial claim. 10
May combine two claims.
Findingown dataThe Nalp3 inflammasome detects both asbestos and silica, and its activation causes IL-1β release.
“Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin 1β secretion.”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
May combine two claims.
Findingown dataDPI and apocynin, which inhibit NADPH oxidase, suppressed ROS production, whereas the mitochondrial inhibitors rotenone and TTFA did not.
“In support of this, ROS production was inhibited by the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin, but not with rotenone (an inhibitor of mitochondrial complex I) or TTFA (an inhibitor of mitochondrial complex II) (fig.S7).”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
May combine two claims.
Findingown dataIn LPS-primed mouse BMDM, zVAD or deficiency in Nalp3 or ASC eliminated caspase-1 cleavage and secretion, and also blocked mature IL-1β processing and release.
“Caspase-1 was no longer cleaved and secreted in the presence of the pan-caspase inhibitor zVAD or in macrophages from Nalp3 and ASC deficient mice and as a consequence, mature IL-1β processing and secretion was abolished (Fig. 2B).”
Quote in the paperSubstantial claim- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
May combine two claims.
Findingown dataDeferoxamine, which chelates iron from asbestos, markedly decreased IL-1β maturation but did not affect MSU.
“We observed that iron chelation of asbestos fibres by deferoxamine strongly reduced IL-1β maturation, whereas it had no effect in response to MSU crystals (Fig. 3E).”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
May combine two claims.
Findingown dataIn mice inhaling asbestos, loss of Nalp3 reduced inflammatory cell recruitment to the lungs and decreased cytokine production.
“In a model of asbestos inhalation, Nalp3 -/-mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production.”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
May combine two claims.
Findingown dataUricase treatment blocked MSU activity but not asbestos.
“On the other hand, uricase treatment blocked the activity of MSU but not of asbestos.”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe Nalp3 inflammasome has been linked to excessive IL-1β in autoinflammatory conditions like Muckle-Wells syndrome and in inflammatory diseases such as gout and pseudogout.
“The Nalp3 inflammasome is implicated in the pathological increase of IL-1β production in autoinflammatory syndromes, such as Muckle-Wells syndrome (22), as well as inflammatory processes, such as gout and pseudogout (7).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDiesel exhaust particles also trigger inflammatory responses.
“Likewise inflammatory responses are observed after exposure to other particulates such as found in diesel exhaust (5).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe results link the Nalp3 inflammasome to pulmonary diseases caused by particulate matter and support its function as a key proinflammatory danger sensor.
“Our findings implicate the Nalp3 inflammasome in particulate matter-related pulmonary diseases and support its role as a major proinflammatory”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
May combine two claims.
Interpretationown dataThe results support a role for the Nalp3 inflammasome in lung inflammatory diseases caused by harmful airborne particles, which can progress to fibrosis and lung cancer.
“Our findings support the implication of the Nalp3 inflammasome in pulmonary inflammatory diseases that are linked to pathogenic air pollutants and can ultimately lead to lung cancer and fibrosis.”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNalp3 can detect endogenous danger signals, including ATP and MSU.
“In addition to PAMPs, Nalp3 has the extraordinary capacity of sensing endogenous stress-associated danger signals (DAMPs) such as ATP (9) or MSU (7).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAsbestos inhalation models show that airway epithelial cells and alveolar macrophages are important in the proliferation, inflammation, and fibrosis caused by asbestos fibres.
“Models of asbestos inhalation have revealed that the airway epithelium and alveolar macrophages play important roles in cell proliferation, inflammation and fibrogenesis triggered by the asbestos fibres (reviewed in (1)).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] source
Not checked in the free run.
May combine two claims.
PremisecitationIron on the surface of crocidolite asbestos makes these fibres especially strong ROS producers, and this iron is believed to contribute to free radical formation.
“Crocidolite asbestos fibres appear to be particularly potent ROS producers due to the presence of iron on the fibre surface.The iron is thought to play an important role in the generation of free radicals (3).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEnvironmental exposure to asbestos fibres has been linked to malignant mesothelioma.
“Asbestos fibres have been associated with development of malignant mesotheliomas after environmental exposures (2).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
Not checked in the free run.
May combine two claims.
Interpretationown dataActin filaments are needed for attempted phagocytosis, but not for the release of mature IL-1β.
“Since the mature form of IL-1β did not accumulate inside the cell (Fig. 3C), we conclude that the actin cytoskeleton is necessary for the attempt to phagocytose, and not to drive mature IL-1β secretion.”
Quote in the paperSubstantial claim- Rests on an assumption: The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationPublished findings indicate that ROS help activate caspase-1 after ATP treatment and contribute to Nalp3 activation by MSU and R837.
“Recent data also suggest a role for ROS in activating caspase-1 upon ATP treatment (18) and in Nalp3 inflammasome activation by MSU and R837 (13).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationSmall particles can be taken up by phagocytic cells, but larger crystals or fibres undergo frustrated phagocytosis and stay at the cell surface.
“Phagocytic cells can endocytose small particles, whereas bigger crystals or fibres are subject to so-called”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOccupational exposure to asbestos or silica can cause lung fibrosis and lung cancer, particularly in smokers.
“Inhalation of asbestos or silica in occupational exposures can result in pulmonary fibrosis (asbestosis, silicosis), and lung cancer, especially in smokers (1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationIL-1β has been proposed to contribute to asbestos-induced mesothelioma by influencing human mesothelial cell growth, and inflammation driven by IL-1β is known to promote tumour development and invasion in vivo.
“An important role for IL-1β has been proposed in the pathogenesis of asbestos-induced mesothelioma by regulating human mesothelial cell proliferation (23) and IL-1β-driven inflammation is well known to promote the development and invasiveness of several tumour types in vivo (24).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [23]
Not checked in the free run.
- cites [24] source
Not checked in the free run.
May combine two claims.
PremisecitationThe Nalp3 inflammasome contains Nalp3, Cardinal, ASC, and caspase-1, and has been linked to mature IL-1β generation after diverse stimuli.
“The Nalp3 inflammasome, composed of the Nod-like receptor (NLR) protein Nalp3 (Cryopyrin/NLRP3), Cardinal, the adaptor ASC and caspase-1, is implicated in the production of mature IL-1β in response to a variety of signals.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] source
Not checked in the free run.
May combine two claims.
Interpretationown dataParticles such as asbestos and MSU, and likely others, turn on the NALP3 inflammasome through a pathway that needs actin-mediated uptake, unlike small soluble activators like R837, ATP, or nigericin.
“Asbestos, MSU and probably other particles activate the NALP3 inflammasome in a similar way, requiring actin-mediated cellular uptake in contrast to small, non-particulate molecules such as R837, ATP or nigericin.”
Quote in the paperSubstantial claim- Rests on an assumption: THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNalp3 detects bacteria through MDP or through bacterial toxins.
“For example, the presence of bacteria is recognized through binding of the pathogen-associated molecular pattern (PAMP) muramyldipeptide (MDP) or via the action of bacterial toxins (9,10).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAsbestos fibres can undergo redox reactions that produce ROS, which are associated with inflammatory and carcinogenic signalling.
“Asbestos fibres have been shown to participate in redox reactions to generate reactive oxygen species (ROS) that are widely linked to signalling pathways causing inflammation and carcinogenesis [reviewed in (17)].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] source
Not checked in the free run.
The paper relies on this without support.
The mouse model of asbestos inhalation reflects the human pulmonary inflammatory response sufficiently to infer human disease mechanisms.
“To investigate the in vivo significance of the Nalp3 inflammasome in asbestos-induced inflammation, Nalp3 -/-and Nalp3 +/+ littermate mice were exposed for 9 days to chrysotile asbestos and markers of injury, inflammation and cytokine production were analysed on day 10.”
“Our findings support the implication of the Nalp3 inflammasome in pulmonary inflammatory diseases that are linked to pathogenic air pollutants and can ultimately lead to lung cancer and fibrosis.”
The paper relies on this without support.
The in vitro concentrations and exposure durations of asbestos and silica used in cell culture are relevant to human exposures.
“THP1 cells were stimulated for 6 h with the indicated amounts (mg/ml media) of asbestos, silica, diesel exhaust particles (DEP), cigarette smoke extract (CSE, in % solution) and MSU.”
“Primary human monocyte-derived macrophages also produced mature IL-1β after stimulation with asbestos or silica (Fig. 1C)”
The paper relies on this without support.
Nalp3-deficient mice lack Nalp3 inflammasome function without compensatory developmental or immunological alterations that affect the measured outcomes.
“Nalp3 -/-and Nalp3 +/+ littermate mice were exposed for 9 days to chrysotile asbestos and markers of injury, inflammation and cytokine production were analysed on day 10.”
“However, significantly fewer cells were recruited to the lungs of Nalp3 -/- mice after exposure to asbestos (Fig. 4A).”
The paper relies on this without support.
The inhibitors used (cytochalasin D, latrunculin A, KCl, NAC, APDC, DPI, apocynin, deferoxamine, uricase) act specifically on their intended targets without off-target effects that explain the results.
“Cytochalasin D inhibited not only secretion of mature IL-1β by asbestos (Fig. 3C), but also by the particulate MSU, while for non-crystalline Nalp3 activators such as R837 and nigericin, IL-1β secretion was not affected (Fig. 3C).”
“IL-1β production was indeed impaired in response to asbestos, MSU and ATP when using these inhibitors (Fig. 3D), suggesting that ROS production was a necessary step in inflammasome activation.”
The paper relies on this without support.
THP1 cells and primary human monocyte-derived macrophages respond to particulate stimulation in a way that represents human alveolar macrophages in vivo.
“We indeed observed that the macrophage-like cell line THP1 secreted mature IL-1β upon stimulation with asbestos or silica (Fig. 1A).”
“Primary human monocyte-derived macrophages also produced mature IL-1β after stimulation with asbestos or silica (Fig. 1C)”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The primed NLRP3 inflammasome can be directly activated by ATP, reactive oxygen species, DNA released from damaged mitochondria, protein aggregates, uric acid crystals, ceramide, bacterial or viral RNA, asbestos, silica, decreased intracellular K+ and Cl− concentrations, and Ca2+ flux.
“In the second, activation step, the now primed NLRP3 inflammasome can be directly activated by any of the various signals including ATP, reactive oxygen species (ROS) and DNA released from damaged mitochondria, protein aggregates, uric acid crystals and ceramide, bacterial or viral RNA, airborne pollutants such as asbestos and silica, decreased intracellular concentrations of K+ and Cl− as well as”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [60]
The paper’s full text (indexed under Abstract; no page supplied) supports NLRP3 activation in response to asbestos, silica, ATP and monosodium urate crystals, and implicates ROS and reduced intracellular K+ in activation. It does not address mitochondrial DNA, protein aggregates, ceramide, bacterial or viral RNA, reduced Cl−, or Ca2+ flux. It also describes direct interaction with NLRP3 as an unresolved hypothesis, rather than establishing direct activation by the listed signals. (LLM, conf=0.90)
Experimental — accuracy not yet measuredmtROS serve as direct activators of the NLRP3 inflammasome.
“These results suggest that mtROS serve as direct activators of the NLRP3 inflammasome.”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [37]
Treatment with ROS inhibitors suppresses cadmium-, silica-, and asbestos-induced NLRP3 inflammasome activation.
“Conversely, treatment with ROS inhibitors has been shown to suppress cadmium‐, silica‐, and asbestos‐induced NLRP3 inflammasome activation.37, 38”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [37]
Inhalation of crystalline silica can induce inflammation by stimulating the NLRP3 inflammasome.
“Inhalation of crystalline silica can induce inflammation by stimulating the NLRP3 inflammasome, a cytosolic receptor complex that plays a critical role in driving inflammatory immune responses.”
From Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages (2018) · cites this paper as [19]
Particulate substances or fibers are likely candidates for the initiation of ROS.
“Particulate substances or fibers are likely candidates for the initiation of ROS (19).”
From Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages (2018) · cites this paper as [19]
In mouse models of sterile injury, such as gout, asbestosis and silicosis, NLRP3-deficient mice exhibited decreased inflammation with reduced levels of tissue infiltration by neutrophils or macrophages.
“Consistently, in mouse models of sterile injury, such as gout, asbestosis and silicosis, NLRP3-deficient mice exhibited decreased inflammation with reduced levels of tissue infiltration by neutrophils or macrophages55,57,58.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [57]
Silica, asbestos and ATP have all been associated with ROS production, and ROS inhibition in vitro resulted in impairment of caspase 1 activation and IL-1β production by these stimuli.
“Silica58,68, asbestos57 and ATP69 have all been associated with ROS production, and ROS inhibition in vitro resulted in impairment of caspase 1 activation and IL-1β production by these stimuli57,58,69.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [57]
Cites
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066 · see citing works
Self-citationGout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326 · see citing works
Self-citationCryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080 · see citing works
Agostini, L., Martinon, F., Burns, K., McDermott, M. F., Hawkins, P. N., & Tschopp, J. (2004) · Immunity · doi:10.1016/s1074-7613(04)00046-9 · Cited by 1,768 · see citing works
Self-citationActivation of the NALP3 inflammasome is triggered by low intracellular potassium concentration
Pétrilli, V, Papin, S., Dostert, C., Mayor, A., Martinon, F., & Tschopp, J. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402195 · Cited by 1,445 · see citing works
Self-citationCytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf
Miao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., Miller, S. I., & Aderem, A. (2006) · Nature Immunology · doi:10.1038/ni1344 · Cited by 1,127 · see citing works
Fernandes-Alnemri, T., Wu, J., Yu, J.-W., Datta, P., Miller, B., Jankowski, W., Rosenberg, S., Zhang, J., & Alnemri, E. S. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402194 · Cited by 1,026 · see citing works
Mechanisms in the Pathogenesis of Asbestosis and Silicosis
MOSSMAN, B. T., & CHURG, A. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.5.9707141 · Cited by 971 · see citing works
Self-citationCruz, C. M., Rinna, A., Forman, H. J., Ventura, A. L. M., Persechini, P. M., & Ojcius, D. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608083200 · Cited by 786 · see citing works
Asbestos: Scientific Developments and Implications for Public Policy
Mossman, B. T., Bignon, J., Corn, M., Seaton, A., & Gee, J. B. L. (1990) · Science · doi:10.1126/science.2153315 · Cited by 742 · see citing works
Self-citationA pilot study of IL-1 inhibition by anakinra in acute gout
So, A., De Smedt, T., Revaz, S., & Tschopp, J. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2143 · Cited by 727 · see citing works
Self-citationInterleukin-1–Receptor Antagonist in the Muckle–Wells Syndrome
Hawkins, P. N., Lachmann, H. J., & McDermott, M. F. (2003) · New England Journal of Medicine · doi:10.1056/nejm200306193482523 · Cited by 654 · see citing works
Identification of Bacterial Muramyl Dipeptide as Activator of the NALP3/Cryopyrin Inflammasome
Martinon, F., Agostini, L., Meylan, E., & Tschopp, J. (2004) · Current Biology · doi:10.1016/j.cub.2004.10.027 · Cited by 579 · see citing works
Self-citationRegulation of Legionella Phagosome Maturation and Infection through Flagellin and Host Ipaf
Amer, A., Franchi, L., Kanneganti, T.-D., Body-Malapel, M., Özören, N., Brady, G., Meshinchi, S., Jagirdar, R., Gewirtz, A., Akira, S., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604933200 · Cited by 453 · see citing works
Franchi, L., Kanneganti, T.-D., Dubyak, G. R., & Núñez, G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610762200 · Cited by 356 · see citing works
The molecular basis of asbestos induced lung injury
Kamp, D. W., & Weitzman, S. A. (1999) · Thorax · doi:10.1136/thx.54.7.638 · Cited by 345 · see citing works
Basic pathogenetic mechanisms in silicosis: current understanding
Rimal, B., Greenberg, A. K., & Rom, W. N. (2005) · Current Opinion in Pulmonary Medicine · doi:10.1097/01.mcp.0000152998.11335.24 · Cited by 326 · see citing works
Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases
Shukla, A., Gulumian, M., Hei, T. K., Kamp, D., Rahman, Q., & Mossman, B. T. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00060-1 · Cited by 288 · see citing works
Self-citationKrelin, Y., Voronov, E., Dotan, S., Elkabets, M., Reich, E., Fogel, M., Huszar, M., Iwakura, Y., Segal, S., Dinarello, C. A., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2956 · Cited by 285 · see citing works
Hansen, K., & Mossman, B. T. (1987) · PubMed · Cited by 227 · see citing works
Self-citationPiguet, P. F., Vesin, C., Grau, G. E., & Thompson, R. C. (1993) · Cytokine · doi:10.1016/1043-4666(93)90024-y · Cited by 215 · see citing works
Robledo, R. F., Buder-Hoffmann, S. A., Cummins, A. B., Walsh, E. S., Taatjes, D. J., & Mossman, B. T. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65001-8 · Cited by 77 · see citing works
Self-citationSabo-Attwood, T., Ramos-Nino, M., Bond, J., Butnor, K. J., Heintz, N., Gruber, A. D., Steele, C., Taatjes, D. J., Vacek, P., & Mossman, B. T. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)61212-6 · Cited by 72 · see citing works
Self-citationCellular and molecular parameters of mesothelioma
Ramos‐Nino, M. E., Testa, J. R., Altomare, D. A., Pass, H. I., Carbone, M., Bocchetta, M., & Mossman, B. T. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20828 · Cited by 71 · see citing works
Self-citationWang, Y., Faux, S., Halldén, G., Kirn, D. H., Houghton, C., Lemoine, N. R., & Patrick, G. (2004) · International Journal of Oncology · doi:10.3892/ijo.25.1.173 · Cited by 53 · see citing works
Haegens, A., Barrett, T. F., Gell, J., Shukla, A., MacPherson, M., Vacek, P., Poynter, M. E., Butnor, K. J., Janssen-Heininger, Y. M., Steele, C., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.3.1800 · Cited by 48 · see citing works
Self-citation
Flagged first, then by citations
1 of the 27 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- K. Hansen, B. T. Mossman, Cancer Res.47, 1681 (1987).
- Y. Wanget al., Int. J. Oncol.25, 173 (2004).
Cited by
Sorted by citations
Immunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755 · see citing works
“Such particles, however, can trigger inflammation through effects on prointerluekin-1β (IL-1β) processing by the inflammasome (Dostert et al., 2008) and this may mediate their tumorigenic activity.”
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931 · see citing works
Brook, R. D., Rajagopalan, S., Pope, C. A., Brook, J. R., Bhatnagar, A., Diez-Roux, A. V., Holguin, F., Hong, Y., Luepker, R. V., Mittleman, M. A., et al. (2010) · Circulation · doi:10.1161/cir.0b013e3181dbece1 · Cited by 6,548 · see citing works
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618 · see citing works
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602 · see citing works
Self-citationSchroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475 · see citing works
“This Review focuses on those PRRs that assemble into high-molecular weight, caspase-1-activating platforms called ‘‘inflamma-somes’’ that control maturation and secretion of interleukins such asIL-1 b and IL-18, whose potent proinflammatory activities direct host responses to infection and injury.”
InfluentialSelf-citationRole of nrf2 in oxidative stress and toxicity
Ma, Q. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140320 · Cited by 4,903 · see citing works
Reactive Oxygen Species in Inflammation and Tissue Injury
Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5149 · Cited by 4,897 · see citing works
“NLRP3 inflammasome, the most well-characterized form, is redox sensitive (99, 379).”
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884 · see citing works
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026 · see citing works
The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation
Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133328 · Cited by 3,539 · see citing works
Pyroptosis: host cell death and inflammation
Bergsbaken, T., Fink, S. L., & Cookson, B. T. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2070 · Cited by 3,185 · see citing works
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049 · see citing works
“Crystalline particles such as asbestos, silica and monosodium urate have been shown to activate the NALP3 inflammasome through ROS generation induced by phagocytic NADPH oxidas”
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065 · see citing works
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Activation and regulation of the inflammasomes
Latz, E., Xiao, T. S., & Stutz, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3452 · Cited by 2,884 · see citing works
Mechanism and Regulation of NLRP3 Inflammasome Activation
He, Y., Hara, H., & Núñez, G. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.09.002 · Cited by 2,759 · see citing works
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708 · see citing works
Self-citationThe NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Vandanmagsar, B., Youm, Y.-H., Ravussin, A., Galgani, J. E., Stadler, K., Mynatt, R. L., Ravussin, E., Stephens, J. M., & Dixit, V. D. (2011) · Nature Medicine · doi:10.1038/nm.2279 · Cited by 2,655 · see citing works
Physiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632 · see citing works
Caspase Functions in Cell Death and DiseasePreprint
McIlwain, D. R., Berger, T., & Mak, T. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008656 · Cited by 2,607 · see citing works
Yunna, C., Mengru, H., Lei, W., & Weidong, C. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173090 · Cited by 2,454 · see citing works
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441 · see citing works
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436 · see citing works
Self-citationInflammasomes in health and disease
Strowig, T., Henao-Mejia, J., Elinav, E., & Flavell, R. (2012) · Nature · doi:10.1038/nature10759 · Cited by 2,230 · see citing works
Nathan, C., & Ding, A. (2010) · Cell · doi:10.1016/j.cell.2010.02.029 · Cited by 2,183 · see citing works
Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production
Saitoh, T., Fujita, N., Jang, M. H., Uematsu, S., Yang, B., Satoh, T., Omori, H., Noda, T., Yamamoto, N., Komatsu, M., et al. (2008) · Nature · doi:10.1038/nature07383 · Cited by 2,020 · see citing works
Targeting the NLRP3 inflammasome in inflammatory diseases
Mangan, M. S. J., Olhava, E. J., Roush, W. R., Seidel, H. M., Glick, G. D., & Latz, E. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.97 · Cited by 1,885 · see citing works
Franchi, L., Eigenbrod, T., Muñoz-Planillo, R., & Nuñez, G. (2009) · Nature Immunology · doi:10.1038/ni.1703 · Cited by 1,834 · see citing works
NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?
Tschopp, J., & Schroder, K. (2010) · Nature reviews. Immunology · doi:10.1038/nri2725 · Cited by 1,859 · see citing works
Self-citationAIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
Fernandes-Alnemri, T., Yu, J.-W., Datta, P., Wu, J., & Alnemri, E. S. (2009) · Nature · doi:10.1038/nature07710 · Cited by 1,831 · see citing works
The roles of TLRs, RLRs and NLRs in pathogen recognition
Kawai, T., & Akira, S. (2009) · International Immunology · doi:10.1093/intimm/dxp017 · Cited by 1,666 · see citing works
Beyond oxidative stress: an immunologist's guide to reactive oxygen species
Nathan, C., & Cunningham-Bussel, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3423 · Cited by 1,619 · see citing works
The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases
Davis, B. K., Wen, H., & Ting, J. P.-Y. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101405 · Cited by 1,618 · see citing works
Molecular mechanisms regulating NLRP3 inflammasome activation
Jo, E.-K., Kim, J. K., Shin, D.-M., & Sasakawa, C. (2016) · Cellular & Molecular Immunology · doi:10.1038/cmi.2015.95 · Cited by 1,378 · see citing works
Ridker, P. M., MacFadyen, J. G., Thuren, T., Everett, B. M., Libby, P., Glynn, R. J., Ridker, P., Lorenzatti, A., Krum, H., Varigos, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)32247-x · Cited by 1,344 · see citing works
Masters, S. L., Dunne, A., Subramanian, S. L., Hull, R. L., Tannahill, G. M., Sharp, F. A., Becker, C., Franchi, L., Yoshihara, E., Chen, Z., et al. (2010) · Nature Immunology · doi:10.1038/ni.1935 · Cited by 1,330 · see citing works
Integrating mechanisms of pulmonary fibrosis
Wynn, T. A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110551 · Cited by 1,282 · see citing works
Innate immunity to virus infection
Takeuchi, O., & Akira, S. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00737.x · Cited by 1,231 · see citing works
Reactive oxygen species and mitochondria: A nexus of cellular homeostasis
Dunn, J. D., Álvarez, L., Zhang, X., & Soldati, T. (2015) · Redox Biology · doi:10.1016/j.redox.2015.09.005 · Cited by 1,199 · see citing works
“Initial studies focused on NOX2 as the relevant ROS source: inhibition or knockdown of NOX2 were found to block IL-1β secretion in response to NLRP3 stimuli [105,109,131].”
BackgroundLeung, C. C., Yu, I. T. S., & Chen, W. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60235-9 · Cited by 1,193 · see citing works
The NLRP3 Inflammasome: A Sensor for Metabolic Danger?
Schroder, K., Zhou, R., & Tschopp, J. (2010) · Science · doi:10.1126/science.1184003 · Cited by 1,131 · see citing works
Self-citationAllen, I. C., Scull, M. A., Moore, C. B., Holl, E. K., McElvania-TeKippe, E., Taxman, D. J., Guthrie, E. H., Pickles, R. J., & Ting, J. P.-Y. (2009) · Immunity · doi:10.1016/j.immuni.2009.02.005 · Cited by 1,113 · see citing works
Regulation of inflammasome activation
Man, S. M., & Kanneganti, T. (2015) · Immunological Reviews · doi:10.1111/imr.12296 · Cited by 1,071 · see citing works
Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease
Masters, S. L., Simon, A., Aksentijevich, I. A., & Kastner, D. L. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141627 · Cited by 1,063 · see citing works
Inflammasome activation and regulation: toward a better understanding of complex mechanisms
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Discovery · doi:10.1038/s41421-020-0167-x · Cited by 1,042 · see citing works
Rajamäki, K., Lappalainen, J., Öörni, K., Välimäki, E., Matikainen, S., Kovanen, P. T., & Eklund, K. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011765 · Cited by 1,039 · see citing works
Sensing and reacting to microbes through the inflammasomes
Franchi, L., Muñoz-Planillo, R., & Núñez, G. (2012) · Nature Immunology · doi:10.1038/ni.2231 · Cited by 1,013 · see citing works
Mitochondria in the Regulation of Innate and Adaptive Immunity
Weinberg, S. E., Sena, L. A., & Chandel, N. S. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.002 · Cited by 960 · see citing works
“Diverse PAMPs and DAMPs such as lipopolysaccharide (LPS), asbestos, ATP, and uric acid lead to NLRP3 activation through increase in ROS (Cruz et al., 2007; Dostert et al., 2008).”
NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis
Grebe, A., Hoss, F., & Latz, E. (2018) · Circulation Research · doi:10.1161/circresaha.118.311362 · Cited by 926 · see citing works
Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?
Abais, J. M., Xia, M., Zhang, Y., Boini, K. M., & Li, P. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5994 · Cited by 936 · see citing works
“The first study of this kind demonstrated inhibited caspase-1 activation and IL-1b release in monocyte THP-1 cells in response to asbestos, MSU, and silica on specific knockdown of NADPH oxidase subunit p22 or use of general ROS scavengers such as N-acetylcysteine and antioxidant ammonium pyrrolidine dithiocarbamate (…”
InfluentialMitochondrial dysfunction in pathophysiology of heart failure
Zhou, B., & Tian, R. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120849 · Cited by 934 · see citing works
Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
Groß, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschläger, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V. L. J., et al. (2009) · Nature · doi:10.1038/nature07965 · Cited by 922 · see citing works
Self-citationMitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation
Iyer, S. S., He, Q., Janczy, J. R., Elliott, E. I., Zhong, Z., Olivier, A. K., Sadler, J. J., Knepper-Adrian, V., Han, R., Qiao, L., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.001 · Cited by 939 · see citing works
Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome
Bauer, C. A., Duewell, P., Mayer, C., Lehr, H. A., Fitzgerald, K. A., Dauer, M., Tschopp, J., Endres, S., Latz, E., & Schnurr, M. M. (2010) · Gut · doi:10.1136/gut.2009.197822 · Cited by 918 · see citing works
Self-citationFunction of Nod‐like receptors in microbial recognition and host defense
Franchi, L., Warner, N. E., Viani, K. L., & Núñez, G. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00734.x · Cited by 900 · see citing works
Kawaguchi, M., Takahashi, M., Hata, T., Kashima, Y., Usui, F., Morimoto, H., Izawa, A., Takahashi, Y., Masumoto, J., Koyama, J., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.982777 · Cited by 884 · see citing works
The Sterile Inflammatory Response
Rock, K. L., Latz, E., Ontiveros, F., & Kono, H. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101311 · Cited by 865 · see citing works
Towards an understanding of the adjuvant action of aluminium
Marrack, P., McKee, A. S., & Munks, M. W. (2009) · Nature Reviews Immunology · doi:10.1038/nri2510 · Cited by 887 · see citing works
“Related reports have shown that other particulate materials, such as silica, asbestos and MSU crystals, also act through the NLRP3 inflammasome to produce IL-1&beta”
DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation
Zindel, J., & Kubes, P. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012419-032847 · Cited by 874 · see citing works
Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome
Misawa, T., Takahama, M., Kozaki, T., Lee, H., Zou, J., Saitoh, T., & Akira, S. (2013) · Nature Immunology · doi:10.1038/ni.2550 · Cited by 863 · see citing works
Bulua, A. C., Simon, A., Maddipati, R., Pelletier, M., Park, H., Kim, K.-Y., Sack, M. N., Kastner, D. L., & Siegel, R. M. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20102049 · Cited by 860 · see citing works
Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis
Moss, B. J., Ryter, S. W., & Rosas, I. O. (2021) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-042320-030240 · Cited by 838 · see citing works
Beutler, B. A. (2009) · Blood · doi:10.1182/blood-2008-07-019307 · Cited by 840 · see citing works
Reactive oxygen species in health and disease
Alfadda, A. A., & Sallam, R. M. (2012) · Journal of Biomedicine and Biotechnology · doi:10.1155/2012/936486 · Cited by 824 · see citing works
The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K. B., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 814 · see citing works
Initiation and perpetuation of <scp>NLRP</scp> 3 inflammasome activation and assembly
Elliott, E. I., & Sutterwala, F. S. (2015) · Immunological Reviews · doi:10.1111/imr.12286 · Cited by 821 · see citing works
Glyburide inhibits the Cryopyrin/Nalp3 inflammasome
Lamkanfi, M., Mueller, J. L., Vitari, A. C., Misaghi, S., Fedorova, A., Deshayes, K., Lee, W. P., Hoffman, H. M., & Dixit, V. M. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200903124 · Cited by 820 · see citing works
Autophagy Controls IL-1β Secretion by Targeting Pro-IL-1β for Degradation
Harris, J., Hartman, M., Roche, C., Zeng, S. G., O'Shea, A., Sharp, F. A., Lambe, E. M., Creagh, E. M., Golenbock, D. T., Tschopp, J., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202911 · Cited by 794 · see citing works
Self-citationGold Nanoparticles of Diameter 1.4 nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage
Pan, Y., Leifert, A., Ruau, D., Neuß, S., Bornemann, J., Schmid, G., Brandau, W., Simon, U., & Jahnen‐Dechent, W. (2009) · Small · doi:10.1002/smll.200900466 · Cited by 802 · see citing works
Mitochondrial reactive oxygen species drive proinflammatory cytokine production
Naik, E., & Dixit, V. M. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110367 · Cited by 783 · see citing works
The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation
Franklin, B. S., Bossaller, L., De Nardo, D., Ratter, J. M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S. R., Al-Amoudi, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2913 · Cited by 773 · see citing works
The inflammasome: an integrated view
Gross, O., Thomas, C. J., Guarda, G., & Tschopp, J. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01046.x · Cited by 778 · see citing works
Self-citationNOD-Like Receptors: Role in Innate Immunity and Inflammatory Disease
Chen, G., Shaw, M. H., Kim, Y., & Núñez, G. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092239 · Cited by 770 · see citing works
The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation
Sharma, D., & Kanneganti, T. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201602089 · Cited by 733 · see citing works
Pattern Recognition Receptors and the Host Cell Death Molecular Machinery
Amarante-Mendes, G. P., Adjemian, S., Branco, L. M., Zanetti, L. C., Weinlich, R., & Bortoluci, K. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02379 · Cited by 759 · see citing works
Synthetic Nanoparticles for Vaccines and Immunotherapy
Irvine, D. J., Hanson, M. C., Rakhra, K., & Tokatlian, T. (2015) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00109 · Cited by 770 · see citing works
Mechanisms of Action of Adjuvants
Awate, S., Babiuk, L. A., & Mutwiri, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00114 · Cited by 741 · see citing works
“Further, blocking ROS using chemical scavengers abolished NLRP3 activation in response to MSU suggesting a link between NLRP3 activation and ROS generation (Dostert et al., 2008).”
The role of oxidative stress during inflammatory processes
Lugrin, J., Rosenblatt‐Velin, N., Parapanov, R., & Liaudet, L. (2013) · Biological Chemistry · doi:10.1515/hsz-2013-0241 · Cited by 742 · see citing works
Abderrazak, A., Syrovets, T., Couchie, D., Hadri, K. E., Friguet, B., Simmet, T., & Rouis, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.008 · Cited by 737 · see citing works
Mechanisms of regulated unconventional protein secretion
Nickel, W., & Rabouille, C. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2617 · Cited by 703 · see citing works
Cao, X. (2015) · Nature reviews. Immunology · doi:10.1038/nri.2015.8 · Cited by 661 · see citing works
Inflammasome activation and IL-1β and IL-18 processing during infection
van de Veerdonk, F. L., Netea, M. G., Dinarello, C. A., & Joosten, L. A. B. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.01.003 · Cited by 693 · see citing works
Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome
Iyer, S. S., Pulskens, W. P., Sadler, J. J., Butter, L. M., Teske, G. J., Ulland, T. K., Eisenbarth, S. C., Florquin, S., Flavell, R. A., Leemans, J. C., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908698106 · Cited by 691 · see citing works
“S5A) 18 .”
Form Follows Function: Nanoparticle Shape and Its Implications for Nanomedicine
Kinnear, C., Moore, T. L., Rodríguez‐Lorenzo, L., Rothen‐Rutishauser, B., & Petri‐Fink, A. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00194 · Cited by 673 · see citing works
NLRP3 Inflammasome and Inflammatory Bowel Disease
Yu, Z., & Zhang, H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00276 · Cited by 659 · see citing works
Sterile inflammation in the liver
Kubes, P., & Mehal, W. Z. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.09.008 · Cited by 666 · see citing works
Liu, J., Han, X., Zhang, T., Tian, K., Li, Z., & Luo, F. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01512-7 · Cited by 718 · see citing works
The role of IL-1β and TNF-α in intervertebral disc degeneration
Wang, Y., Che, M., Xin, J., Zheng, Z. J., Li, J., & Zhang, S. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110660 · Cited by 626 · see citing works
Functions of ROS in Macrophages and Antimicrobial Immunity
Herb, M., & Schramm, M. (2021) · Antioxidants · doi:10.3390/antiox10020313 · Cited by 633 · see citing works
Walsh, J. G., Muruve, D. A., & Power, C. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3638 · Cited by 637 · see citing works
Influenza virus activates inflammasomes via its intracellular M2 ion channel
Ichinohe, T., Pang, I. K., & Iwasaki, A. (2010) · Nature Immunology · doi:10.1038/ni.1861 · Cited by 632 · see citing works
“In addition, lysosomal membrane damage caused by phagocytosis of crystals such as asbestos, silica and aluminum salt triggers NLRP3 activatio”
Li, N., Zhou, H., Wu, H., Wu, Q., Duan, M., Deng, W., & Tang, Q. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101215 · Cited by 595 · see citing works
Bauernfeind, F., Bartok, E., Rieger, A., Franchi, L., Núñez, G., & Hornung, V. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100613 · Cited by 617 · see citing works
The signal pathways and treatment of cytokine storm in COVID-19
Yang, L., Xie, X., Tu, Z., Fu, J., Xu, D., & Zhou, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00679-0 · Cited by 599 · see citing works
Kool, M., Pétrilli, V., Smedt, T. D., Rolaz, A., Hammad, H., van Nimwegen, M., Bergen, I. M., Castillo, R., Lambrecht, B. N., & Tschopp, J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.6.3755 · Cited by 612 · see citing works
Self-citationSignaling by ROS drives inflammasome activation
Martinon, F. (2010) · European Journal of Immunology · doi:10.1002/eji.200940168 · Cited by 604 · see citing works
Zheng, M., & Kanneganti, T. (2020) · Immunological Reviews · doi:10.1111/imr.12909 · Cited by 591 · see citing works
Tetherin Inhibits HIV-1 Release by Directly Tethering Virions to Cells
Pérez-Caballero, D., Zang, T. M., Ebrahimi, A., McNatt, M. W., Gregory, D. A., Johnson, M. C., & Bieniasz, P. D. (2009) · Cell · doi:10.1016/j.cell.2009.08.039 · Cited by 590 · see citing works
The NLRP3 Inflammasome Promotes Renal Inflammation and Contributes to CKD
Vilaysane, A., Chun, J., Seamone, M. E., Wang, W., Chin, R., Hirota, S., Li, Y., Clark, S. A., Tschopp, J., Trpkov, K., et al. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010020143 · Cited by 587 · see citing works
Self-citation
- Authors
- Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J.
- Affiliations
- University of Vermont (US)
- Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
- Venue
- Science
- Published
- 2008-05-02
- Volume
- 320
- Issue
- 5876
- Pages
- 674-677
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2396588
- OpenAlex
- W2009004909
- Semantic Scholar
- d21a1e75f0ab181b382438ef2083584a4de9f54b
- Cited by
- 2,658
- References
- 27
- Citations by year
- 2026: 57 · 2025: 76 · 2024: 126 · 2023: 121 · 2022: 131 · 2021: 140 · 2020: 168 · 2019: 154 · 2018: 154 · 2017: 166 · 2016: 168 · 2015: 169 · 2014: 187 · 2013: 192 · 2012: 171
- FWCI
- 64.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (5p01ca114047-05)
- National Heart, Lung, and Blood Institute (P01HL067004, P01 HL67004)
- National Cancer Institute (P01CA-114047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- NLRP3 inflammasome, asbestos, silica, innate immune activation, IL-1β, reactive oxygen species, NADPH oxidase, phagocytosis, lung inflammation, pulmonary fibrosis, lung cancer, particulate matter
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Asbestos, Carrier Proteins, Humans, Immunity, Inflammation, Macrophages, Silicon Dioxide, Inflammation Mediators, Mice, Interleukin-1beta
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
