title: Resveratrol inhibits the acetylated α-tubulin-mediated assembly of the NLRP3-inflammasome.
abstract: With its adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Nod-like receptor family, pyrin domain containing 3 (NLRP3) forms the inflammasome and mediates inflammatory innate immune responses. Development of an anti-inflammatory drug targeting the NLRP3-inflammasome is urgently required because its aberrant activation often causes inflammatory diseases, including gout. We show that resveratrol, a natural polyphenol in grapes and wine, is a safe and effective phytochemical that inhibits NLRP3-inflammasome activation. Resveratrol inhibits the accumulation of acetylated α-tubulin caused by mitochondrial damage in macrophages stimulated with inducers of the NLRP3-inflammasome. Consequently, resveratrol inhibits the acetylated-α-tubulin-mediated spatial arrangement of mitochondria and their subsequent contact with the endoplasmic reticulum (ER), causing insufficient assembly of ASC on the mitochondria and NLRP3 on the ER. These findings indicate that resveratrol targets the generation of an optimal site for the assembly of NLRP3 and ASC, thus inhibiting NLRP3-inflammasome activation. Therefore, resveratrol could be an effective medication for the treatment of NLRP3-related inflammatory diseases.
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Takuma
authors: T
authors: Misawa
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Tatsuya
authors: T
authors: Saitoh
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Tatsuya
authors: T
authors: Kozaki
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Sehoon
authors: S
authors: Park
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Michihiro
authors: M
authors: Takahama
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Shizuo
authors: S
authors: Akira
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D064209:Phytochemicals / Q000494:pharmacology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*; D027843:Vitis / Q000737:chemistry; D014920:Wine
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D064209:Phytochemicals; D013267:Stilbenes; D014404:Tubulin; D020169:Caspases; D000077185:Resveratrol
keywords: cytokine; inflammasome; innate immunity; microtubule