TRPM2 links oxidative stress to NLRP3 inflammasome activation Journal Article

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Authors: Zhong, Z.; Zhai, Y.; Liang, S.; Mori, Y.; Han, R.; Sutterwala, F. S.; Qiao, L
Article Title: TRPM2 links oxidative stress to NLRP3 inflammasome activation
Abstract: Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin-1beta secretion to initiate undesirable inflammatory responses that are associated with both autoinflammatory and metabolic diseases. Although mitochondrial reactive oxygen species have a central role in NLRP3 inflammasome activation, how reactive oxygen species signal assembly of the NLRP3 inflammasome remains elusive. Here, we identify liposomes as novel activators of the NLRP3 inflammasome and further demonstrate that liposome-induced inflammasome activation also requires mitochondrial reactive oxygen species. Moreover, we find that stimulation with liposomes/crystals induced reactive oxygen species-dependent calcium influx via the TRPM2 channel and that macrophages deficient in TRPM2 display drastically impaired NLRP3 inflammasome activation and interleukin-1beta secretion. Consistently, Trpm2(-/-) mice are resistant to crystal-/liposome-induced interleukin-1beta-mediated peritonitis in vivo. Together, these results identify TRPM2 as a key factor that links oxidative stress to the NLRP3 inflammasome activation. Therefore, targeting TRPM2 may be effective for the treatment of NLRP3 inflammasome-associated inflammatory disorders.
Journal Title: Nature communications
Volume: 4
ISSN: 2041-1723; 2041-1723
Publisher: Unknown  
Journal Place: England
Date Published: 2013
Start Page: 1611
Language: eng
DOI/URL:

10.1038/ncomms2608

10.1038/ncomms2608
Notes: ID: 12961; GR: AI087630/AI/NIAID NIH HHS/United States; GR: DE019075/DE/NIDCR NIH HHS/United States; GR: R01 AI087630/AI/NIAID NIH HHS/United States; JID: 101528555; NIHMS446435; OID: NLM: NIHMS446435 [Available on 09/19/13]; OID: NLM: PMC3605705 [Available on 09/19/13]; PMCR: 2013/09/19 00:00; 2012/10/16 [received]; 2013/02/14 [accepted]; ppublish