Proceedings of the National Academy of Sciences - PNAS, 2012-07, Vol.109 (28), p.11282-11287
2012
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- Autor(en) / Beteiligte
- Titel
- Critical role for calcium mobilization in activation of the NLRP3 inflammasome
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-07, Vol.109 (28), p.11282-11287
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) inflammasome mediates production of inflammatory mediators, such as IL-1β and IL-18, and as such is implicated in a variety of inflammatory processes, including infection, sepsis, autoinflammatory diseases, and metabolic diseases. The proximal steps in NLRP3 inflammasome activation are not well understood. Here we elucidate a critical role for Ca ²⁺ mobilization in activation of the NLRP3 inflammasome by multiple stimuli. We demonstrate that blocking Ca ²⁺ mobilization inhibits assembly and activation of the NLRP3 inflammasome complex, and that during ATP stimulation Ca ²⁺ signaling is pivotal in promoting mitochondrial damage. C/EPB homologous protein, a transcription factor that can modulate Ca ²⁺ release from the endoplasmic reticulum, amplifies NLRP3 inflammasome activation, thus linking endoplasmic reticulum stress to activation of the NLRP3 inflammasome. Our findings support a model for NLRP3 inflammasome activation by Ca ²⁺-mediated mitochondrial damage.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1117765109Titel-ID: cdi_fao_agris_US201600129002
- Format
- –
- Schlagworte
- adenosine triphosphate, Adenosine Triphosphate - metabolism, Animals, Biological Sciences, Calcium, Calcium - metabolism, Carrier Proteins - metabolism, CCAAT-Enhancer-Binding Proteins - metabolism, DNA damage, endoplasmic reticulum, Endoplasmic Reticulum - metabolism, Epithelial cells, Flow Cytometry - methods, Gene expression regulation, Immunity, Innate, Inflammasomes - metabolism, Inflammation, Inflammation - metabolism, Inflammatory diseases, interleukin-18, interleukin-1beta, Membranes, metabolic diseases, Mice, Mice, Transgenic, Mitochondria, Mitochondria - metabolism, Mitochondrial DNA, Models, Biological, Natural killer cells, NLR Family, Pyrin Domain-Containing 3 Protein, Physiological regulation, Proteins, Receptors, sepsis (infection), Signal Transduction, T lymphocytes, transcription factors