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Kang, Kwi Young; Kim, Young-Kyun; Yi, Hyoju; Kim, Juryun; Jung, Hae-Rin; Kim, In Je; Cho, Jae-Hyoung; Park, Sung-Hwan; Kim, Ho-Youn; Ju, Ji Hyeon
International immunopharmacology, 20/May , Volume: 16, Issue: 1Journal Article
This study was undertaken to determine whether metformin has anti-inflammatory effects in the collagen antibody-induced arthritis (CAIA) murine model. The effect of metformin on Th17 cell differentiation was also investigated. CAIA mice were treated with 100 and 150mg/kgi.p. metformin (low- and high-dose groups, respectively). Arthritis activity and histological joint destruction were studied. Flow cytometry was used to (i) determine RORγt-expressing CD4+ percentages in draining axillary lymph nodes (ALNs) from metformin-treated and untreated mice with CAIA, (ii) determine Th17 percentages in splenic CD4+ T cells cultured ex vivo for 3days in Th17-differentiation-inducing conditions, and (iii) determine the percentages of RORγt+CD4+ T cells when normal splenic T cells from DBA/1 mice were cultured in Th17-differentiation-inducing conditions together with various metformin doses. Western blot analysis was used to assess the intracellular signaling of the metformin-treated splenocytes. Metformin attenuated both arthritis scores and bone destruction in CAIA mice, decreased the serum levels of the pro-inflammatory cytokines, TNF-α and IL-1, and reduced the number of RORγt+CD4+ T cells in the ALNs. Splenocytes from metformin-treated CAIA mice differentiated less readily into Th17 cells upon ex vivo stimulation. Metformin treatment of normal cells cultured in Th17-differentiation-inducing conditions decreased the number of RORγt-expressing CD4+ cells in a dose-dependent manner and downregulated STAT3 phosphorylation via the AMPK pathway. Metformin had an anti-inflammatory effect on murine autoimmune arthritis due to the inhibition of Th17 cell differentiation. Metformin may have a possible therapeutic value for treatment of rheumatoid arthritis. •Metformin attenuated both arthritis scores and bone destruction in murine autoimmune arthritis.•Metformin inhibited Th17 cell differentiation in vivo.•Metformin treatment decreased the number of RORγt-expressing CD4+ cells in a dose-dependent manner.
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