Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming
| Autor: | David Brough, Pablo Pelegrín, Shi Yu, Gloria Lopez-Castejon, Catherine B. Lawrence, Fátima Martín-Sánchez, Jack Peter Green |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Lydia Becker Institute Inflammasomes Interleukin-1beta Caspase 1 Priming (immunology) Inflammation Proinflammatory cytokine Mice 03 medical and health sciences Chlorides ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation NLR Family Pyrin Domain-Containing 3 Protein medicine Animals NIMA-Related Kinases Secretion Caspase Mice Knockout Ion Transport Multidisciplinary integumentary system biology Chemistry Inflammasome Cell biology CARD Signaling Adaptor Proteins 030104 developmental biology PNAS Plus Potassium biology.protein Female Efflux Protein Multimerization medicine.symptom medicine.drug |
| Zdroj: | Green, J, Yu, S, Martín-Sánchez, F, Pelegrin, P, Lopez-Castejon, G, Lawrence, C B & Brough, D 2018, ' Chloride regulates dynamic NLRP3-dependent ASC oligomerisation and inflammasome priming ', Proceedings of the National Academy of Sciences, vol. 115, no. 40, pp. E9371-E9380 . https://doi.org/10.1073/pnas.1812744115 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1812744115 |
| Popis: | The NLRP3 inflammasome is an important regulator of inflammation and immunity. It is a multimolecular platform formed within cells that facilitates the activation of proinflammatory caspases to drive secretion of cytokines such as interleukin-1β (IL-1β). Knowledge of the mechanisms regulating formation of the NLRP3 inflammasome is incomplete. Here we report Cl(−) channel-dependent formation of dynamic ASC oligomers and inflammasome specks that remain inactive in the absence of K(+) efflux. Formed after Cl(−) efflux exclusively, ASC specks are NLRP3 dependent, reversible, and inactive, although they further prime inflammatory responses, accelerating and enhancing release of IL-1β in response to a K(+) efflux-inducing stimulus. NEK7 is a specific K(+) sensor and does not associate with NLRP3 under conditions stimulating exclusively Cl(−) efflux, but does after K(+) efflux, activating the complex driving inflammation. Our investigation delivers mechanistic understanding into inflammasome activation and the regulation of inflammatory responses. |
| Databáze: | OpenAIRE |
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