Paeoniflorin besylate relieves mice with antigen-induced experimental Sjogren's syndrome by regulating GRK2-JAK1-STAT1/2 signaling pathway / 中国药理学通报

ABSTRACT

Aim To observe the effect of CP-25 on the ESS mouse model and establish whether its effect is through regulating the binding of GRK2 to JAK1 and inhibiting the JAK1-STAT1/2-CXCL13 signaling pathway. Method We established ESS mouse model induced by SG protein, established into normal group, model group, CP-25 group with concentration of 35 mg • kg"1, 70 mg • kg"1, and HCQ group with concentration of 80 mg • kg"1. Mouse saliva flow was measured. The infiltration of lymphocyte in SG was observed by HE staining. The expression of p-JAKl, p- STAT1 and p-STAT2 in submandibular gland tissue was detected by Western blot. The level of CXCL13 in SG of mice was tested by IHC. GRK2 and JAK1 binding was determined by immunofluorescence and CO- IP. Results Compared with normal group, the saliva flow rate of ESS mice was low and lymphocytes were significantly infiltrated in the submandibular gland pathological sections. The CXCL13 protein level was highly expressed, which activated the JAK1-STAT1/2 signal. CP-25 significantly increased the salivary flow rate in ESS mice, reduced lymphocyte infiltration, improved pathological abnormalities, and inhibited the expression of JAK1-STAT 1/2 signaling and CXCL13. CP-25 significantly promoted the binding of GRK2 to JAK1. Conclusions CP-25 may inhibit the binding of GRK2 to JAK1, and then inhibit the activation of JAK1-STAT1/2-CXCL13 signaling pathway, improve the abnormal pathological manifestations of lymphocyte infiltration in submandibular gland, and improve the rate of saliva flow. CP-25 plays a therapeutic role in ESS mice.