JAK1-STAT3 blockade by JAK inhibitor SHR0302 attenuates inflammatory responses of adjuvant-induced arthritis rats via inhibiting Thl7 and total B cells  

出　　处：《中国药理学通报》2015年第B11期31-32,共2页Chinese Pharmacological Bulletin

摘　　要：Aim To investigate the effects of JAK inhibitor （SHR0302） on adjuvant-induced arthritis （AA） rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 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 nag · kg^-1, ig） and MTX （0.5 nag · kg^-1 , ig） . The effects of SHR0302 on 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; Thl7, Treg, total B and memory B cell proportion was measured by flow cytometry; Cytokines TNF-αβ, IL-1β, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by ELISA kits; The ex- pression of p-JAK1 and p-STAT3 was measured by Western blot analysis. Results SHR0302 suppressed the se- verity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and allevia- ted histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Thl7 and total B, and inhibited JAK1-STAT3 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 signifi- cantly reducing Thl7 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation.

关 键 词：JAK INHIBITOR adjuvant-induced ARTHRITIS THL7 Treg memory B cells STAT3 

分 类 号：R[医药卫生]