ER stress activates the NLRP3 inflammasome via an UPR-independent pathway |
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| Authors: | P Menu A Mayor R Zhou A Tardivel H Ichijo K Mori J Tschopp |
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| Affiliation: | 1Department of Biochemistry, University of Lausanne, Epalinges, Switzerland;2Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China;3Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan;4Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan |
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| Abstract: | Uncontrolled endoplasmic reticulum (ER) stress responses are proposed to contribute to the pathology of chronic inflammatory diseases such as type 2 diabetes or atherosclerosis. However, the connection between ER stress and inflammation remains largely unexplored. Here, we show that ER stress causes activation of the NLRP3 inflammasome, with subsequent release of the pro-inflammatory cytokine interleukin-1β. This ER-triggered proinflammatory signal shares the same requirement for reactive oxygen species production and potassium efflux compared with other known NLRP3 inflammasome activators, but is independent of the classical unfolded protein response (UPR). We thus propose that the NLRP3 inflammasome senses and responds to ER stress downstream of a previously uncharacterized ER stress response signaling pathway distinct from the UPR, thus providing mechanistic insight to the link between ER stress and chronic inflammatory diseases. |
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| Keywords: | endoplasmic reticulum stress NLRP3 inflammasome innate immunity macrophages |
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