ABSTRACT
Objective:To explore the effect of the synthetic immunomodulator CH 2b with a thiazolidin-4-one ring on the pathogenesis of rheumatoid arthritis (RA) mice induced by glucose-6-phosphate isomerase(GPI) mixed peptides.Methods:hGPI325-339 ,hGPI469-483 peptide fragments were mixed with complete freund′s adjuvant fully ,DBA/1 mice were givien subcutaneous injection of the emulsifiers,pertussis toxin to strengthen immunity.And then RA mice were intervened with α-GalCer and CH2b,the changes of body weight ,ankle joint symptoms scores were observed .The joint tissues stained with hematoxylin and eosin ( HE) was used to evaluate the inflammatory cells.Fluorescence-activated cell sorting ( FACS) was used to detect the frequency changes of iNKT cells .Cytometric bead array(CBA) was used to analyze the levels of serum cytokines TNF-α,IL-6,IL-4,IFN-γ.Results: Compared with the model group,α-GalCer,CH2b could reduce the inflammation of the model mice ,significantly improve the body weight growth and the joint swelling(P0.05).Conclusion:Immunomodulator CH2b by activating iNKT cells affect the secretion of inflammatory cytokines ,and it relieved the GPI induced arthritis .
ABSTRACT
[ ABSTRACT] AIM:To establish an animal model of rheumatoid arthritis ( RA) in DBA/1 mice induced by im-munodominant mixed peptides derived from glucose-6-phosphate isomerase (GPI).METHODS: The DBA/1 mice were immunized with emulsified mixed peptide fragments of hGPI 325-339+hGPI469-483 or single peptide hGPI325-339 in com-plete Freund′s adjuvant by subcutaneous injection to induce the model of RA .Body weight , ankle joint symptom scores , the pathological change of the ankle joint , the levels of CD4 +T cells in the spleen and peripheral blood , the proportion of iNKT cells in the peripheral blood , and the levels of TNF-αand IL-6 in serum were detected to evaluate and analyze the model.RESULTS:The hind paw of the model mice appeared red swelling on the 8th day, and then aggravated gradually to the limbs.The red swelling reached peak on the 14th day, and then relieved gradually .Inflammation response dominated by lymphocytes and monocytes was observed in the ankle joint .The inflammatory effect of mixed peptides was more obvious than that of the single one (P<0.05).Compared with control group and the mice treated with single peptide , the weight gain was slow, the amount of CD4 +T cells in the peripheral blood and spleen were increased , the proportion of peripheral iNKT cells in the inflammatory peak was decreased (P<0.05), and the serum level of TNF-αwas increased significantly ( P<0.05) in the mice treated with mixed peptide fragments .CONCLUSION: The immunological characteristics of RA model induced by mixed GPI peptides in DBA/1 mice is closer to that in RA patients , especially in the immunopathology of iNKT cells.Therefore, this model can be used as a new tool for studying the mechanism and immunological intervention of RA.