Posttreatment of Maresin1 Inhibits NLRP3 inflammasome activation via promotion of NLRP3 ubiquitination.

Maresin1 is a potent lipid mediator exhibiting potential anti-inflammatory activity in a variety of inflammatory diseases, however, the underlying mechanisms remain poorly understood. Excessive activation of NLRP3 inflammasome has been established in multiple inflammatory diseases. Here, we show that Maresin1 dose-dependently inhibited the NLRP3 inflammasome activation and subsequent caspase-1 activation and IL-1β secretion. This inhibitory effect could be reversed by KH7 and H89, the inhibitors of the cAMP-PKA signaling pathway. Activation of PKA kinase induced by Maresin1 led to the K63-linked ubiquitination of NLRP3 in macrophages. Maresin1 attenuated serum IL-1β secretion through inhibition of NLRP3 inflammasome in vivo using Nlrp3-deficient mouse models of lipopolysaccharide (LPS)-induced sepsis. Maresin1 also repressed MSU-induced peritonitis. This study suggests that Maresin1 is an inhibitor of NLRP3 inflammasome activation and can be used clinically in the treatment of NLRP3 inflammasome-driven inflammatory diseases. © 2020 Federation of American Societies for Experimental Biology.

Citation

Sisi Zheng, Minqi Ma, Zhongwang Li, Yu Hao, Hui Li, Panhan Fu, Shengwei Jin. Posttreatment of Maresin1 Inhibits NLRP3 inflammasome activation via promotion of NLRP3 ubiquitination. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020 Sep;34(9):11944-11956

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PMID: 32667092

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