Sterile inflammation: sensing and reacting to damage

In the paper

“The sterile inflammation that ensues either resolves the initial insult or leads to disease.”

In the paper

“However, uric acid depletion does not completely eliminate acetaminophen-induced liver inflammation or the adjuvant activity of damaged cells, which may reflect residual uric acid following depletion or redundant activities by other DAMPs.”

What the sources say

• Not checked yetcites [13] Kono, H., Chen, C. J., Ontiveros, F. & Rock, K. L. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J. Clin. Invest. 120, 1939–1949 (2010). source

In the paper

“Tlr2 and Tlr4 double-knockout mice exhibit impaired transepithelial recruitment of inflammatory cells and decreased survival in response to lung injury31.”

What the sources say

• Not checked yetcites [31] Jiang, D. et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nature Med. 11, 1173–1179 (2005). This paper shows the dual role of TLRs in mediating sterile inflammation in response to hyaluronan fragments released during injury and in promoting tissue repair. source

In the paper

“by contrast, in particulate-induced sterile inflammation, uric acid depletion had no effect, suggesting that uric acid may be a major pro-inflammatory DAMP that is specifically involved in cell death-related sterile inflammation13.”

What the sources say

• Not checked yetcites [13] Kono, H., Chen, C. J., Ontiveros, F. & Rock, K. L. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J. Clin. Invest. 120, 1939–1949 (2010). source

In the paper

“TLR4, specifically, has been shown to mediate inflammatory responses to free fatty acids, which are elevated in obesity and are associated with insulin resistance38.”

What the sources say

• Not checked yetcites [38] Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015–3025 (2006). source

In the paper

“Similarly, TLR3 can sense endogenous RNA derived from necrotic neutrophils, which contributes to the inflammatory response elicited by necrosis in the bowel39.”

What the sources say

• Not checked yetcites [39] Cavassani, K. A. et al. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J. Exp. Med. 205, 2609–2621 (2008). source

In the paper

“Although these factors are not conventionally considered as DAMPs, they can mediate sterile inflammatory responses (see below).”

In the paper

“Thus, understanding the mechanisms of sterile inflammation is important for devising treatment strategies against various human diseases.”

In the paper

“based on our current understanding, we propose three, not necessarily mutually exclusive, mechanisms by which sterile endogenous stimuli trigger inflammation: activation of PRRs by mechanisms similar to those used by microorganisms and PAMPs; release of intracellular cytokines and chemokines, such as IL-1α, that activate common pathways downstream of PRRs; and direct activation by receptors that”

In the paper

“It is now evident that PRRs also recognize non-infectious material that can cause tissue damage and endogenous molecules that are released during cellular injury (TABLE 1).”

What the sources say

• Not checked yetcites TABLE 1

In the paper

“Finally, immune cell infiltration in the absence of microorganisms is also characteristic of tumours, and these cells can influence the growth and progression of cancer6.”

What the sources say

• Not checked yetcites [6] Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002). source

In the paper

“DAMPs have been identified by their ability to induce inflammatory responses in vitro and/orin vivo when purified and by the observed reduction in inflammation when they are selectively depleted17.”

What the sources say

• Not checked yetcites [17] Kono, H. & Rock, K. L. How dying cells alert the immune system to danger. Nature Rev. Immunol. 8, 279–289 (2008). source

In the paper

“Interestingly, the anti-diabetic drug glyburide (Glibenclamide; Roche/Sanofi-Aventis) has been shown to block glucose-mediated secretion of IL-1β by mouse pancreatic islets62, as well as IL-1β production by macrophages in response to IAPP61, and NLRP3-deficient mice were more glucose tolerant than wild-type mice62.”

What the sources say

• Not checked yetcites [61] Masters, S. L. et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nature Immunol. 11, 897–904 (2010). source
• Not checked yetcites [62] Zhou, R., Tardivel, A., Thorens, B., Choi, I. & Tschopp, J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nature Immunol. 11, 136–140 (2010). source

In the paper

“Importantly, NLRP3-dependent caspase 1 activation was associated with destabilization of the lysosomal membrane and activation of lysosomal proteases (specifically, cathepsin b)44.”

What the sources say

• Not checked yetcites [44] Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol. 9, 847–856 (2008). This study was pivotal in providing a model of NLRP3 activation that involves lysosomal damage and cathepsin B activation. source

In the paper

“Compared with wild-type mice, IL-1R-deficient mice had decreased neutrophilic infiltration and inflammation in the liver after acetaminophen-induced liver injury22 and in the lungs after exposure to silica44.”

What the sources say

• Not checked yetcites [22] Chen, C. J. et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nature Med. 13, 851–856 (2007). This paper demonstrates a crucial role for IL-1α in sterile inflammation and, in particular, neutrophil recruitment induced by necrotic cells. source
• Not checked yetcites [44] Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol. 9, 847–856 (2008). This study was pivotal in providing a model of NLRP3 activation that involves lysosomal damage and cathepsin B activation. source

In the paper

“NLRP3 signalling has been shown to involve at least two steps, the first involving PRR- or cytokine-dependent transcriptional upregulation of NLRP3 and the second involving activation of the NLRP3 inflammasome, which leads to IL-1β production53,54 (BOX 4).”

What the sources say

• Not checked yetcites [53] Bauernfeind, F. G. et al. Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 183, 787–791 (2009). source
• Not checked yetcites [54] Franchi, L., Eigenbrod, T. & Nunez, G. Cutting edge: TNF-α mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J. Immunol. 183, 792–796 (2009). References 53 and 54 provide evidence that the first signal, or priming event, necessary for activation of the NLRP3 inflammasome involves upregulation of NLRP3 expression by NF-κB through the action of TLRs or pro-inflammatory cytokines such as TNF. source

In the paper

“Furthermore, TLRs seem to function redundantly with other signalling pathways, so the contribution of TLRs to the overall sterile inflammatory response remains unclear.”

In the paper

“However, the amounts of ATP necessary for NLRP3-mediated caspase 1 activation to be detected in macrophages in vitro are greater than physiological concentrations63 and, therefore, the relevance of this pathway in vivo is uncertain.”

What the sources say

• Not checked yetcites [63] el-Moatassim, C. & Dubyak, G. R. A novel pathway for the activation of phospholipase D by P2z purinergic receptors in BAC1.2F5 macrophages. J. Biol. Chem. 267, 23664–23673 (1992). source

In the paper

“elevated levels of IL-1β are also observed in the pancreatic islet cells from patients with type 2 diabetes46, which is increasingly being recognized as having a strong inflammatory component47.”

What the sources say

• Not checked yetcites [46] Boni-Schnetzler, M. et al. Increased interleukin (IL)-1β messenger ribonucleic acid expression in β-cells of individuals with type 2 diabetes and regulation of IL-1β in human islets by glucose and autostimulation. J. Clin. Endocrinol. Metab. 93, 4065–4074 (2008). source
• Not checked yetcites [47] Shoelson, S. E., Lee, J. & Goldfine, A. B. Inflammation and insulin resistance. J. Clin. Invest. 116, 1793–1801 (2006). source

In the paper

“Thus, it has been suggested that NLRP3 senses intracellular K + depletion, which may act as a surrogate marker of cellular injury that is sensed by NLRP3.”

In the paper

“However, IL-1β secretion was only partially dependent on P2RX7, suggesting that the release of ATP may be only one mechanism by which necrotic cells can activate NLRP3.”

What the sources say

• Not checked yetcites [60] Iyer, S. S. et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl Acad. Sci. USA 106, 20388–20393 (2009). source

In the paper

“ATP binds to purinergic receptor P2X7 (P2RX7), which leads to the opening of an ATP-gated cation channel that induces K + efflux and the formation of a large pore mediated by the hemichannel protein pannexin 1 (REFS 64,65).”

What the sources say

• Not checked yetcites [64] Pelegrin, P. & Surprenant, A. Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor. EMBO J. 25, 5071–5082 (2006). source
• Not checked yetcites [65] Locovei, S., Wang, J. & Dahl, G. Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett. 580, 239–244 (2006). source

In the paper

“In atherosclerosis, engulfment of cholesterol by macrophages leads to IL-1β production, which can stimulate the production of platelet-derived growth factor, promotion of smooth muscle cell and fibroblast proliferation, arterial wall thickening and plaque formation5,45.”

What the sources say

• Not checked yetcites [5] Ross, R. Atherosclerosis — an inflammatory disease. N. Engl. J. Med. 340, 115–126 (1999). source
• Not checked yetcites [45] Raines, E. W., Dower, S. K. & Ross, R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 243, 393–396 (1989). source

In the paper

“Collectively, the evidence suggests that endogenous stimuli can induce a sterile inflammatory response through TLRs, although the precise molecules that engage TLRs remain poorly defined.”

In the paper

“IL-1β is a potent pro-inflammatory cytokine that is produced mainly by macrophages and has many biological functions that are important in sterile inflammation, such as the upregulation of those adhesion molecules on endothelial cells that are important for the recruitment of neutrophils and monocytes42 and for the induction of additional pro-inflammatory mediators43.”

What the sources say

• Not checked yetcites [42] Wang, X., Feuerstein, G. Z., Gu, J. L., Lysko, P. G. & Yue, T. L. Interleukin-1β induces expression of adhesion molecules in human vascular smooth muscle cells and enhances adhesion of leukocytes to smooth muscle cells. Atherosclerosis 115, 89–98 (1995). source
• Not checked yetcites [43] Gabay, C., Lamacchia, C. & Palmer, G. IL-1 pathways in inflammation and human diseases. Nature Rev. Rheumatol. 6, 232–241 (2010). source

In the paper

“Low-density lipoprotein (LDL) receptor-deficient mice, which are prone to developing atherosclerotic lesions, had lower IL-1β levels, smaller atherosclerotic lesions and less neutrophilic infiltration than wild-type mice when lethally irradiated and infused with NLRP3-deficient bone marrow59.”

What the sources say

• Not checked yetcites [59] Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357–1361 (2010). source

In the paper

“IL-1, which includes both IL-1α and IL-1β, is a key mediator of sterile inflammation that acts through the IL-1 receptor (IL-1R)22,41.”

What the sources say

• Not checked yetcites [22] Chen, C. J. et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nature Med. 13, 851–856 (2007). This paper demonstrates a crucial role for IL-1α in sterile inflammation and, in particular, neutrophil recruitment induced by necrotic cells. source
• Not checked yetcites [41] Kono, H., Karmarkar, D., Iwakura, Y. & Rock, K. L. Identification of the cellular sensor that stimulates the inflammatory response to sterile cell death. J. Immunol. 184, 4470–4478 (2010). This study shows the crucial role for macrophages in mediating the inflammatory response to sterile cell death, such as by IL-1α production. source

In the paper

“Lysosomal damage can occur during cellular injury and necrosis, and has also been associated with other sterile activators of NLRP3, such as cholesterol59 and silica crystals44.”

What the sources say

• Not checked yetcites [59] Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357–1361 (2010). source
• Not checked yetcites [44] Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol. 9, 847–856 (2008). This study was pivotal in providing a model of NLRP3 activation that involves lysosomal damage and cathepsin B activation. source

In the paper

“NLRP3-deficient mice were also less susceptible to renal ischaemia–reperfusion injuries induced by bilateral renal artery ligation and to acetaminophen-induced hepatotoxicity40,60.”

What the sources say

• Not checked yetcites [40] Imaeda, A. B. et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J. Clin. Invest. 119, 305–314 (2009).
• Not checked yetcites [60] Iyer, S. S. et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl Acad. Sci. USA 106, 20388–20393 (2009). source

In the paper

“In general, the ligands of these CLRs are unknown70.”

What the sources say

• Not checked yetcites [70] Geijtenbeek, T. B. & Gringhuis, S. I. Signalling through C-type lectin receptors: shaping immune responses. Nature Rev. Immunol. 9, 465–479 (2009). source

In the paper

“This class of PRRs contains a carbohydrate-binding domain that recognizes carbohydrates on viruses, bacteria and fungi.”

In the paper

“Using a model of peritonitis triggered by necrotic cells, IL-1α was shown to be important for the recruitment of neutrophils, which was caspase 1 independent, and this response was impaired in mice lacking IL-1R expression by non-myeloid cells22.”

What the sources say

• Not checked yetcites [22] Chen, C. J. et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nature Med. 13, 851–856 (2007). This paper demonstrates a crucial role for IL-1α in sterile inflammation and, in particular, neutrophil recruitment induced by necrotic cells. source

In the paper

“CLRs are an increasingly recognized category of PRRs that are important in host defence.”

In the paper

“In particular, C-type lectin 4e (CLeC4e; also known as MINCLe) can detect the DAMP spliceosome-associated protein 130 (SAP130), which is a component of a small nuclear ribonucleo protein that can be released by necrotic but not apoptotic cells, resulting in upregulation of pro-inflammatory mediators such as CXC-chemokine ligand 2 (CXCL2) and in neutrophil recruitment73.”

What the sources say

• Not checked yetcites [73] Cambi, A. & Figdor, C. Necrosis: C-type lectins sense cell death. Curr. Biol. 19, R375–R378 (2009). source

In the paper

“Therefore, it may be involved in regulating sterile immune responses, although the specific ligand recognized in this case is still unknown73,75.”

What the sources say

• Not checked yetcites [73] Cambi, A. & Figdor, C. Necrosis: C-type lectins sense cell death. Curr. Biol. 19, R375–R378 (2009). source
• Not checked yetcites [75] Sancho, D. et al. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458, 899–903 (2009). This paper showed a role for CLEC9A in regulating immune responses to sterile cell death, specifically through the cross-presentation of dead cell-associated antigens. source

In the paper

“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.”

What the sources say

• Not checked yetcites [57] Dostert, C. et al. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320, 674–677 (2008). This study led to the model of NLRP3 activation that is dependent on the sensing of ROS, and demonstrated a role for NLRP3 in asbestosis. source
• Not checked yetcites [58] Cassel, S. L. et al. The Nalp3 inflammasome is essential for the development of silicosis. Proc. Natl Acad. Sci. USA 105, 9035–9040 (2008). source
• Not checked yetcites [68] Fubini, B. & Hubbard, A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic. Biol. Med. 34, 1507–1516 (2003). source

In the paper

“evidence to support this are the observations that artificial lysosomal rupture alone can activate NLRP3 and that pharmacological inhibition or genetic depletion of cathepsin b results in inhibition of caspase 1 activation, although this inhibition was only partial44,56,59.”

What the sources say

• Not checked yetcites [44] Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol. 9, 847–856 (2008). This study was pivotal in providing a model of NLRP3 activation that involves lysosomal damage and cathepsin B activation. source
• Not checked yetcites [56] Halle, A. et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nature Immunol. 9, 857–865 (2008). source
• Not checked yetcites [59] Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357–1361 (2010). source

In the paper

“Collectively, there is still controversy regarding the roles of the individual model pathways for NLRP3 activation, and it remains to be determined whether there is a common mechanism by which numerous heterogeneous stimuli converge on NLRP3.”

In the paper

“when cells die by necrosis, such as during injury, this precursor form of IL-1α is released, leading to activation of its cognate receptor and rapid recruitment of inflammatory cells into the surrounding injured tissue22,78.”

What the sources say

• Not checked yetcites [22] Chen, C. J. et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nature Med. 13, 851–856 (2007). This paper demonstrates a crucial role for IL-1α in sterile inflammation and, in particular, neutrophil recruitment induced by necrotic cells. source
• Not checked yetcites [78] Cohen, I. et al. Differential release of chromatin-bound IL-1α discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc. Natl Acad. Sci. USA 107, 2574–2579 (2010). source

In the paper

“Therefore, it is possible that divergent upstream danger signals that are sensed by NLRP3 may converge on lysosomal damage and cathepsin b activation.”

In the paper

“Unlike its related family members IL-1β and IL-18, IL-1α is synthesized as a biologically active cytokine in its full-length precursor form and does not require processing for signalling through IL-1R78,79.”

What the sources say

• Not checked yetcites [78] Cohen, I. et al. Differential release of chromatin-bound IL-1α discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc. Natl Acad. Sci. USA 107, 2574–2579 (2010). source
• Not checked yetcites [79] Dinarello, C. A. IL-1: discoveries, controversies and future directions. Eur. J. Immunol. 40, 599–606 (2010). source

In the paper

“In this study, TXNIP-deficient mice had impaired IL-1β production and neutrophil influx after intraperitoneal injection of MSU crystals, and TXNIP-deficient macrophages had decreased IL-1β production in response to a range of known NLRP3 activators, including MSU crystals, silica, and ATP62.”

What the sources say

• Not checked yetcites [62] Zhou, R., Tardivel, A., Thorens, B., Choi, I. & Tschopp, J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nature Immunol. 11, 136–140 (2010). source

In the paper

“This is in contrast with apoptotic cells, in which IL-1α is sequestered intracellularly78, or with intact cells, in which the secretion of mature IL-1α is partially dependent on caspase 1 activity80–82.”

What the sources say

• Not checked yetcites [78] Cohen, I. et al. Differential release of chromatin-bound IL-1α discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc. Natl Acad. Sci. USA 107, 2574–2579 (2010). source
• Not checked yetcites [80] Li, P. et al. Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock. Cell 80, 401–411 (1995). source
• Not checked yetcites [81] Kuida, K. et al. Altered cytokine export and apoptosis in mice deficient in interleukin-1β converting enzyme. Science 267, 2000–2003 (1995). source
• Not checked yetcites [82] Keller, M., Ruegg, A., Werner, S. & Beer, H. D. Active caspase-1 is a regulator of unconventional protein secretion. Cell 132, 818–831 (2008). source

In the paper

“CLeC9A has been shown to recognize necrotic cells and induce the cross-presentation of dead cell-associated antigens to CD8+ T cells.”

What the sources say

• Not checked yetcites [73] Cambi, A. & Figdor, C. Necrosis: C-type lectins sense cell death. Curr. Biol. 19, R375–R378 (2009). source
• Not checked yetcites [75] Sancho, D. et al. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458, 899–903 (2009). This paper showed a role for CLEC9A in regulating immune responses to sterile cell death, specifically through the cross-presentation of dead cell-associated antigens. source

In the paper

“These products can accumulate under conditions of high oxidant stress and are found at elevated levels in chronic inflammatory disease states such as type 1 diabetes92.”

What the sources say

• Not checked yetcites [92] Bucciarelli, L. G. et al. RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. Cell. Mol. Life Sci. 59, 1117–1128 (2002). source

In the paper

“Apoe–/–Rage–/– mice also exhibited a reduction in atherosclerosis101, as shown by a reduction in both atherosclerotic plaque formation and production of pro-inflammatory mediators within the aorta.”

What the sources say

• Not checked yetcites [101] Harja, E. et al. Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE−/− mice. J. Clin. Invest. 118, 183–194 (2008). source

In the paper

“In addition to AGes, RAGe also recognizes HMGb193 and the S100 family members19, which are released during cellular stress and necrotic cell death, and β-amyloid94, the accumulation of which is pathogenic in Alzheimer's disease.”

What the sources say

• Not checked yetcites [94] Yan, S. D. et al. RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease. Nature 382, 685–691 (1996). source

In the paper

“Thus, the release of IL-1α from certain cells, such as dendritic cells, contributes to sterile inflammation, but macrophages seem to be the primary sentinel cells that mediate the sensing of necrotic cells through the production of mature IL-1α and IL-1β41.”

What the sources say

• Not checked yetcites [41] Kono, H., Karmarkar, D., Iwakura, Y. & Rock, K. L. Identification of the cellular sensor that stimulates the inflammatory response to sterile cell death. J. Immunol. 184, 4470–4478 (2010). This study shows the crucial role for macrophages in mediating the inflammatory response to sterile cell death, such as by IL-1α production. source

In the paper

“Collectively, the evidence suggests that the precursor forms of IL-1α and IL-33 (both of which are biologically active) are preferentially released during necrosis to alert the immune system to cell damage, leading to the initiation of the healing response.”

In the paper

“These studies suggest that the precursor form of IL-1α that is released by necrotic cells contributes to the initial neutrophilic response, but resident macrophages are the main source of mature IL-1α and IL-1β, which are needed for cell death-induced sterile inflammation (FIG. 3).”

In the paper

“Thus, IL-33, which is expressed at high levels by endothelial cells and some epithelial cells, is expected to be active when it is released during necrosis, but not apoptosis, which is associated with executioner caspase activation.”

In the paper

“How CD44 signalling contributes to sterile inflammation is unclear, but it has been shown to physically interact with TLR4 in vitro and function as an accessory molecule for TLR4 signalling in response to hyaluronan102,103.”

What the sources say

• Not checked yetcites [102] Jiang, D., Liang, J. & Noble, P. W. Hyaluronan in tissue injury and repair. Annu. Rev. Cell Dev. Biol. 23, 435–461 (2007). source
• Not checked yetcites [103] Taylor, K. R. et al. Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2. J. Biol. Chem. 282, 18265–18275 (2007). source

In the paper

“In addition to AGes, RAGe also recognizes HMGb193 and the S100 family members19, which are released during cellular stress and necrotic cell death, and β-amyloid94, the accumulation of which is pathogenic in Alzheimer's disease.”

What the sources say

• Not checked yetcites [19] Hofmann, M. A. et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97, 889–901 (1999). source
• Not checked yetcites [93] Hori, O. et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J. Biol. Chem. 270, 25752–25761 (1995). source

In the paper

“CD24-mediated inhibition was associated with increased pro-inflammatory cytokine production by HMGb1 and decreased survival following acetaminophen-induced liver injury106.”

What the sources say

• Not checked yetcites [106] Chen, G. Y., Tang, J., Zheng, P. & Liu, Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323, 1722–1725 (2009). source

In the paper

“Those treated with anakinra had improved glucose levels and reduced systemic inflammation, as suggested by lower circulating levels of inflammatory markers, such as IL-6 and C-reactive protein.”

What the sources say

• Not checked yetcites [109] Larsen, C. M. et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356, 1517–1526 (2007). source

In the paper

“Similarly, CD36 is a scavenger receptor that binds oxidized LDL and β-amyloid, which are associated with sterile inflammation related to atherosclerosis and Alzheimer's disease, respectively.”

What the sources say

• Not checked yetcites [104] Hoebe, K. et al. CD36 is a sensor of diacylglycerides. Nature 433, 523–527 (2005). source

In the paper

“Indeed, mice deficient in TLR2 and TLR4 expression had increased mortality in response to hypoxia-induced lung injury, which was associated with decreased integrity of the lung epithelium31.”

What the sources say

• Not checked yetcites [31] Jiang, D. et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nature Med. 11, 1173–1179 (2005). This paper shows the dual role of TLRs in mediating sterile inflammation in response to hyaluronan fragments released during injury and in promoting tissue repair. source

In the paper

“TLR4 signalling was found to be important for dendritic cell-mediated cross-presentation of tumour antigens from dying, chemotherapy-treated tumour cells and involved HMGb1 release from the dying cells115.”

What the sources say

• Not checked yetcites [115] Apetoh, L. et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature Med. 13, 1050–1059 (2007). This paper showed the importance of TLR4 signalling in response to DAMPs derived from tumour cell death after chemotherapy or radiation treatment during the induction of host immune responses that are important for inhibiting tumour growth. source

In the paper

“Furthermore, chemotherapy-treated tumour cells injected into wild-type mice inhibited tumour development when the mice were rechallenged with tumour cells, but this effect was abrogated in NLRP3-deficient and P2RX7-deficient mice112, suggesting that NLRP3-mediated IL-1β production through the ATP–P2RX7 pathway is important for immune surveillance against tumours.”

What the sources say

• Not checked yetcites [112] Ghiringhelli, F. et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nature Med. 15, 1170–1178 (2009). source

In the paper

“However, the clinical study was still small and was not designed to determine optimal dosing, duration of use or long-term outcomes in disease control.”

What the sources say

• Not checked yetcites [109] Larsen, C. M. et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356, 1517–1526 (2007). source

In the paper

“Similarly, CD36 is a scavenger receptor that binds oxidized LDL and β-amyloid, which are associated with sterile inflammation related to atherosclerosis and Alzheimer's disease, respectively.”