title: Sirt2 suppresses inflammatory responses in collagen-induced arthritis.
abstract: Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD(+)-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.
authors.affiliation: Department of Orthopaedics, Qilu Hospital, Shandong University, 44# Wenhua Xi Road, Jinan, Shandong 250012, PR China; Department of Orthopaedics, Yantaishan Hospital, 91# Jiefang Road, Yantai, Shandong 264001, PR China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Lin
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Chuanqiang
authors.initials: C
authors.lastname: Jiang
authors.forename: Huanyu
authors.initials: H
authors.lastname: Hong
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000107:Acetylation; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D012720:Severity of Illness Index; D056565:Sirtuin 2 / Q000235:genetics / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016207:Cytokines; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2
keywords: Acetylation; Arthritis; Inflammation; NF-κB; Sirt2