Mucosal administration of altered CⅡ263-272 peptide inhibits collagen-induced arthritis / 北京大学学报(医学版)

ABSTRACT

Objective:To evaluate the effect of mucosal administration of altered collagen Ⅱ(CⅡ)263-272 peptide(267Q→A,270K→A and 271G→A) on collagen induced arthritis(CIA),and to explore the mechanism of the inhibitory effect of the altered CⅡ263-272 peptide on CIA.Methods:CIA was induced in Lewis rats by immunization with bovine CⅡ.Altered CⅡ263-272 peptide was given intranasally beginning from the onset of arthritis(100 ?g/dose,daily for 5 doses and continuing every other day for other 7 doses).Wild CⅡ263-272 peptide(100 ?g/dose) or PBS was administered as controls with the same procedure.Therapeutic effects were evaluated by arthritis scores,body weight change,and joint pathologic scores.The anti-CⅡ antibody and its subtypes were measured with ELISA.The cytokines of IFN-? and IL-10 were measured with ELISA.The induction of regulatory T cells was assessed by FACS analysis of percentage of peripheral CD4+CD25+ T cells,and by real-time PCR analysis of the expression of Foxp3 and TGF-? mRNA.Results:(1) Following treatment with the altered CⅡ263-272 peptide,arthiritis scores were reduced and body weight was increased.The mean arthritis scores of rats treated with altered peptide,wild peptide and PBS were 2.50?2.43,4.50?2.23 and 6.33?2.73,respectively.The altered peptide could retard the histologic lesion of the joints.(2) The titers of anti-CⅡ antibodies IgG and IgG1 in the three groups were similar,but the IgG2a in altered peptide-treated rats decreased markedly as compared with PBS-treated rats(0.56?0.19 vs 0.95?0.29,P