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Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration
Abstract
Inflammasomes are Nod-like receptor(NLR)- and caspase-1-containing cytoplasmic multiprotein complexes, which upon their assembly, process and activate the proinflammatory cytokines interleukin (IL)-1beta and IL-18. The inflammasomes harboring the NLR members NALP1, NALP3 and IPAF have been best characterized. While the IPAF inflammasome is activated by bacterial flagellin, activation of the NALP3 inflammasome is triggered not only by several microbial components, but also by a plethora of danger-associated host molecules such as uric acid. How NALP3 senses these chemically unrelated activators is not known. Here, we provide evidence that activation of NALP3, but not of the IPAF inflammasome, is blocked by inhibiting K(+) efflux from cells. Low intracellular K(+) is also a requirement for NALP1 inflammasome activation by lethal toxin of Bacillus anthracis. In vitro, NALP inflammasome assembly and caspase-1 recruitment occurs spontaneously at K(+) concentrations below 90 mM, but is prevented at higher concentrations. Thus, low intracellular K(+) may be the least common trigger of NALP-inflammasome activation.
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“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).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [13]
In the citing paper
“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).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [13]
In the citing paper
“Decreased K+ levels in the cytosolic microenvironment may lead to NLRP3 inflammasome assembly and activation through NIMA-related serine/threonine kinase 7 (Nek7) binding, which culminates in the secretion of inflammatory cytokines, such as IL-1β and IL-18 [151,152]”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [152]
In the citing paper
“Consistently, inhibition of K+ efflux by high extracellular K+ concentrations prevents NLRP3-dependent caspase 1 activation in response to ATP, asbestos, silica and MSU crystals58,66.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [66]
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Self-citation
Metadata
- Authors
- Pétrilli, V, Papin, S., Dostert, C., Mayor, A., Martinon, F., & Tschopp, J.
- Affiliations
- University of Lausanne (CH)
- Harvard University (US)
- Corresponding author
- Tschopp, J
- Venue
- Cell Death & Differentiation
- Published
- 2007-06-29
- Volume
- 14
- Issue
- 9
- Pages
- 1583-1589
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1978274182
- Cited by
- 1,445
- References
- 38
- Citations by year
- 2026: 36 · 2025: 54 · 2024: 62 · 2023: 71 · 2022: 85 · 2021: 78 · 2020: 102 · 2019: 86 · 2018: 73 · 2017: 104 · 2016: 70 · 2015: 79 · 2014: 90 · 2013: 101 · 2012: 93
- FWCI
- 25.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- NLRP3 inflammasome, potassium efflux, intracellular potassium concentration, caspase-1 activation, inflammasome assembly, NOD-like receptors, damage-associated molecular patterns, uric acid, IL-1β, IL-18
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Calcium-Binding Proteins, Carrier Proteins, Cell Line, Humans, Inflammation, Mice, Inbred BALB C, Mice, Inbred C57BL, Potassium, Macrophages, Peritoneal, Caspase 1, Interleukin-18, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins, Interleukin-1beta
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