[The cytokine homeostasis was regulated by over-expression of Sirt1 in collagen-induced arthritis mice].

Objective: To investigate the effects of over-expression of Sirt1 on cytokines in the collagen type 2-induced arthritis (CIA) mice.

Methods: The female DBA/1 mouse CIA model was established by subcutaneous injection of collagen type 2. Recombinant adenovirus carrying Sirt1 gene was infected into CIA mice through tail vein injection. The effects of over-expression of Sirt1 on CIA mice were assessed by measuring arthritis index. The serum levels of cytokines including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), IL-17, IL-4 and IL-10 in CIA mice were examined by ELISA. The mRNA levels of Sirt1, matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by real-time quantitative PCR (qRT-PCR). The protein levels of NF-κB subunit p65 and acetylated p65 were determined by Western blotting.

Results: Compared with control groups, over-expression of Sirt1 significantly ameliorated the symptoms of arthritis in CIA mouse. Furthermore, proinflammatory factors (IL-1β, TNF-α, IL-17) decreased while anti-inflammatory factors (IL-4 and IL-10) increased in CIA mice. The over-expression of Sirt1 significantly down-regulated MMP-13 mRNA level and up-regulated TIMP-1 mRNA level. Additionally, the over-expressed Sirt1 reduced acetylation of p65.

Conclusion: Over-expression of Sirt1 may regulate the balance of cytokines in CIA mice.