JAK1-STAT3 blockade by JAK inhibitor SHR0302attenuates inflammatory responses of adjuvant-induced ar

来源 :中国药理学会第十三次全国学术大会 | 被引量 : 0次 | 上传用户:yuhang0211
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  Aim To investigate the effects of JAK inhibitor (SHR0302) on adjuvantinduced arthritis (AA) rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1STAT3 pathway, including Thl7,Treg, total B cells and memory B cells.Methods Animals were divided randomly into 6 groups including normal control, AA, SHR0302 (0.3, 1.0, 3.0 mg · kg1, ig) and MTX (0.5 mg · kg1, ig).The effects of SHR0302on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen, inflammatory cytokine and antibody production in serum.We examined the proliferation of T, B and FLS by CCK8 kit; Th17, Treg, total B and memory B cell proportion was measured by flow cytometry; Cytokines TNFα, IL1β, IL10, IL17 and antibody IgG1, IgG2a levels in serum were measured by ELISA kits; The expression of pJAK1 and pSTAT3 was measured by Western blot analysis.Results SHR0302 suppressed the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats.SHR0302 can inhibit the proliferation of T, B and FLS, and downregulated cytokines TNFα, IL1β, IL17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Th17 and total B, and inhibited JAK1STAT3 phosphorylation; There was no significant effect on Treg function and memory B cell proportion.Conclusion SHR0302 may attenuate the severity of AA rats, partially through significandy reducing Th17 function and total B cell proportion by inhibiting JAK1STAT3 phosphorylation.
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