Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/ncomms2608
Keywords
-
Categories
Funding
- National Institutes of Health [DE019075, AI087630]
- American Heart Association [10SDG4140138]
- Muscular Dystrophy Association [MDA171667]
Ask authors/readers for more resources
Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin-1 beta 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-1 beta secretion. Consistently, Trpm2(-/-) mice are resistant to crystal-/liposome-induced interleukin-1 beta-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available