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Aim To study the effect of gender differences in C57BL / 6J mice on antigen induced Sjogren's syndrome(SS)model. Methods The submandibular gland protein of C57BL/6J female and male mice was extracted and mixed with the same amount of Freund's complete adjuvant(FCA)for the first three times, the antigen concentration was adjusted to 2.5 g·L-1, mixed with Freund's incomplete adjuvant(FIA)for the fourth time, and the same-sex mouse antigen was injected into the back of mice for a total of four times to induce the mouse SS model. The mouse SS model was induced by multi-point intradermal injection of antigen on the back of mice for four times,the body weight of female and male mice was measured every week, the general condition was observed, the saliva volume of mice was measured at the sixth week of modeling. After the mice were sacrificed, the pathological changes of submandibular gland and the changes of T and B lymphocyte subsets in spleen were detected, and the differences in SS model preparation between female and male mice were compared. Results The SS model of male and female mice was successfully established, and there was no significant difference in general condition, saliva volume, submandibular gland pathology, plasma cells and memory B cells between male and female SS mice. The success rate of SS model was 75% in female mice and 60% in male mice. Compared with normal mice of the same sex, the weight loss of female SS mice was earlier and more obvious than that of male SS mice; the submandibular gland index of male mice was significantly higher than that of female mice. Compared with normal mice of the same sex, the proportion of Th17 and Treg cells in spleen of female SS mice was more statistically significant than that of male SS mice. Conclusions The success rate of SS modeling in female mice is higher than that in male mice. Compared with male SS mice, female SS mice have more significant SS like manifestations and pathological manifestations, which can provide a reference basis for the selection of gender when establishing SS model.
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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.
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Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical manifestations and complex pathogenesis, characterized by loss of immune tolerance to autoantigens and production of large amounts of autoantibodies. Interferon (I F N) signaling pathway is one of the pathogenetic pathways widely recognized at present. In recent years, the correlation between IFN signaling and epigenetic modification in the occurrence and development of SLE has beena research hotspot. And in this paper, the relevant studies are reviewed in order to provide new research ideas for the pathogenesis of SLE.