1. Posttreatment of Maresin1 Inhibits NLRP3 inflammasome activation via promotion of NLRP3 ubiquitination
- Author
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Yu Hao, Minqi Ma, Sisi Zheng, Hui Li, Shengwei Jin, Zhongwang Li, and Pan-Han Fu
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Proteasome Endopeptidase Complex ,Docosahexaenoic Acids ,Lipopolysaccharide ,Inflammasomes ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ubiquitin ,In vivo ,Sepsis ,NLR Family, Pyrin Domain-Containing 3 Protein ,Genetics ,medicine ,Animals ,Secretion ,Molecular Biology ,Mice, Knockout ,integumentary system ,biology ,Chemistry ,Kinase ,Ubiquitination ,Inflammasome ,Lipid signaling ,Cell biology ,Enzyme Activation ,030104 developmental biology ,biology.protein ,Signal transduction ,030217 neurology & neurosurgery ,Biotechnology ,medicine.drug - Abstract
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.
- Published
- 2020