Critical role for calcium mobilization in activation of the NLRP3 inflammasome
| Autor: | Aldebaran M. Hofer, Jiujiu Yu, Tomohiko Murakami, Aisleen McColl, Tiffany Horng, Vanessa Byles, Johan Öckinger |
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| Rok vydání: | 2012 |
| Předmět: |
Inflammasomes
Mice Transgenic Mitochondrion Biology Endoplasmic Reticulum Pyrin domain Models Biological AIM2 Mice Adenosine Triphosphate NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Transcription factor Inflammation Multidisciplinary integumentary system Endoplasmic reticulum Inflammasome Biological Sciences Flow Cytometry Immunity Innate Cell biology Mitochondria CCAAT-Enhancer-Binding Proteins Calcium Signal transduction Carrier Proteins NLRP3 inflammasome complex medicine.drug Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 109(28) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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