TRPM2 links oxidative stress to NLRP3 inflammasome activation

Zhenyu Zhong, Yougang Zhai, Shuang Liang, Yasuo Mori, Renzhi Han, Fayyaz S. Sutterwala, Liang Qiao

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin-1β 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-1β secretion. Consistently, Trpm2 -/- mice are resistant to crystal-/liposome- induced interleukin-1β-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.

Original languageEnglish (US)
Article number1611
JournalNature communications
Volume4
DOIs
StatePublished - Apr 11 2013
Externally publishedYes

Fingerprint

Inflammasomes
Oxidative stress
interleukins
Oxidative Stress
Chemical activation
activation
secretions
oxygen
Liposomes
metabolic diseases
Reactive Oxygen Species
Interleukin-1
crystals
macrophages
stimulation
particulates
Crystals
mice
calcium
assembly

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

TRPM2 links oxidative stress to NLRP3 inflammasome activation. / Zhong, Zhenyu; Zhai, Yougang; Liang, Shuang; Mori, Yasuo; Han, Renzhi; Sutterwala, Fayyaz S.; Qiao, Liang.

In: Nature communications, Vol. 4, 1611, 11.04.2013.

Research output: Contribution to journalArticle

Zhong, Zhenyu ; Zhai, Yougang ; Liang, Shuang ; Mori, Yasuo ; Han, Renzhi ; Sutterwala, Fayyaz S. ; Qiao, Liang. / TRPM2 links oxidative stress to NLRP3 inflammasome activation. In: Nature communications. 2013 ; Vol. 4.
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