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TRPM2 links oxidative stress to the NLRP3 inflammasome activation

Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin 1β (IL-1β) secretion to initiate undesirable inflammatory responses that are associated with both autoinflammatory and metabolic diseases. Although mitochondrial reactiv...

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Autores principales: Zhong, Zhenyu, Zhai, Yougang, Liang, Shuang, Mori, Yasuo, Han, Renzhi, Sutterwala, Fayyaz S, Qiao, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605705/
https://www.ncbi.nlm.nih.gov/pubmed/23511475
http://dx.doi.org/10.1038/ncomms2608
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author Zhong, Zhenyu
Zhai, Yougang
Liang, Shuang
Mori, Yasuo
Han, Renzhi
Sutterwala, Fayyaz S
Qiao, Liang
author_facet Zhong, Zhenyu
Zhai, Yougang
Liang, Shuang
Mori, Yasuo
Han, Renzhi
Sutterwala, Fayyaz S
Qiao, Liang
author_sort Zhong, Zhenyu
collection PubMed
description Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin 1β (IL-1β) secretion to initiate undesirable inflammatory responses that are associated with both autoinflammatory and metabolic diseases. Although mitochondrial reactive oxygen species (ROS) play a central role in NLRP3 inflammasome activation, how ROS signal assembly of the NLRP3 inflammasome remains elusive. Here, we identify liposomes as novel activators of NLRP3 inflammasome and further demonstrate that liposome-induced inflammasome activation also requires mitochondrial ROS. Moreover, we found that stimulation with liposomes/crystals induced ROS-dependent calcium influx via the TRPM2 channel and that macrophages deficient in TRPM2 displayed drastically impaired NLRP3 inflammasome activation and IL-1β secretion. Consistently, Trpm2(−/−) mice were resistant to crystal-/liposome-induced IL-1β-mediated peritonitis in vivo. Together, these results identify TRPM2 as a key player that links oxidative stress to the NLRP3 inflammasome activation. Therefore, targeting TRPM2 may be effective for the treatment of NLRP3 inflamamsome-associated inflammatory disorders.
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spelling pubmed-36057052013-09-19 TRPM2 links oxidative stress to the NLRP3 inflammasome activation Zhong, Zhenyu Zhai, Yougang Liang, Shuang Mori, Yasuo Han, Renzhi Sutterwala, Fayyaz S Qiao, Liang Nat Commun Article Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin 1β (IL-1β) secretion to initiate undesirable inflammatory responses that are associated with both autoinflammatory and metabolic diseases. Although mitochondrial reactive oxygen species (ROS) play a central role in NLRP3 inflammasome activation, how ROS signal assembly of the NLRP3 inflammasome remains elusive. Here, we identify liposomes as novel activators of NLRP3 inflammasome and further demonstrate that liposome-induced inflammasome activation also requires mitochondrial ROS. Moreover, we found that stimulation with liposomes/crystals induced ROS-dependent calcium influx via the TRPM2 channel and that macrophages deficient in TRPM2 displayed drastically impaired NLRP3 inflammasome activation and IL-1β secretion. Consistently, Trpm2(−/−) mice were resistant to crystal-/liposome-induced IL-1β-mediated peritonitis in vivo. Together, these results identify TRPM2 as a key player that links oxidative stress to the NLRP3 inflammasome activation. Therefore, targeting TRPM2 may be effective for the treatment of NLRP3 inflamamsome-associated inflammatory disorders. 2013 /pmc/articles/PMC3605705/ /pubmed/23511475 http://dx.doi.org/10.1038/ncomms2608 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zhong, Zhenyu
Zhai, Yougang
Liang, Shuang
Mori, Yasuo
Han, Renzhi
Sutterwala, Fayyaz S
Qiao, Liang
TRPM2 links oxidative stress to the NLRP3 inflammasome activation
title TRPM2 links oxidative stress to the NLRP3 inflammasome activation
title_full TRPM2 links oxidative stress to the NLRP3 inflammasome activation
title_fullStr TRPM2 links oxidative stress to the NLRP3 inflammasome activation
title_full_unstemmed TRPM2 links oxidative stress to the NLRP3 inflammasome activation
title_short TRPM2 links oxidative stress to the NLRP3 inflammasome activation
title_sort trpm2 links oxidative stress to the nlrp3 inflammasome activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605705/
https://www.ncbi.nlm.nih.gov/pubmed/23511475
http://dx.doi.org/10.1038/ncomms2608
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