title: Resveratrol inhibits NLRP3 inflammasome activation by preserving mitochondrial integrity and augmenting autophagy.
abstract: The NLRP3 inflammasome is a caspase-1-containing multi-protein complex that controls the release of IL-1β and plays important roles in the development of inflammatory disease. Here, we report that resveratrol, a polyphenolic compound naturally produced by plants, inhibits NLRP3 inflammasome-derived IL-1β secretion and pyroptosis in macrophages. Resveratrol inhibits the activation step of the NLRP3 inflammasome by suppressing mitochondrial damage. Resveratrol also induces autophagy by activating p38, and macrophages treated with an autophagy inhibitor are resistant to the suppressive effects of resveratrol. In addition, resveratrol administration mitigates glomerular proliferation, glomerular sclerosis, and glomerular inflammation in a mouse model of progressive IgA nephropathy. These findings were associated with decreased renal mononuclear leukocyte infiltration, reduced renal superoxide anion levels, and inhibited renal NLRP3 inflammasome activation. Our data indicate that resveratrol suppresses NLRP3 inflammasome activation by preserving mitochondrial integrity and by augmenting autophagy.
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Chang
authors.forename: Shuk-Man
authors.initials: SM
authors.lastname: Ka
authors.forename: Wan-Han
authors.initials: WH
authors.lastname: Hsu
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
authors.forename: Louis Kuoping
authors.initials: LK
authors.lastname: Chao
authors.forename: Chai-Ching
authors.initials: CC
authors.lastname: Lin
authors.forename: Cho-Chen
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chen
authors.forename: Huan-Wen
authors.initials: HW
authors.lastname: Chiu
authors.forename: Chen-Lung
authors.initials: CL
authors.lastname: Ho
authors.forename: Yi-Chich
authors.initials: YC
authors.lastname: Chiu
authors.forename: May-Lan
authors.initials: ML
authors.lastname: Liu
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; C529636:NALP1 protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D020170:Caspase 1; D000077185:Resveratrol