Effect of multiple amino acid substitutions of collagen Ⅱ 263-272 on collagen-induced arthritis
- VernacularTitle:Ⅱ型胶原多肽263~272序列中多个氨基酸替换的意义及其在胶原性关节炎治疗中的作用
- Author:
Ru LI
;
Xia LI
- Publication Type:Journal Article
- Keywords:
Collagen type Ⅱ;
Arthritis,rheumatoid;
Immunotherapy
- From:
Journal of Peking University(Health Sciences)
2003;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To evaluate the effect of multiple amino acid substitutions of CⅡ263-272 peptide on collagen-induced arthritis,and explore a therapeutic strategy of rheumatoid arthritis.Methods: A panel of altered CⅡ263-272 peptides was synthesized with substitutions of TCR-contact residues of CⅡ263-272 with alanine.The competitive inhibition of APL to wild type CⅡ263-272 was analyzed by ~3H incorporation assay.CIA model was induced by intradermal injection of bovine CⅡ.Altered CⅡ peptide was injected subcutaneously in different doses(1,10,100 ?g,respectively,twice per week) after onset of CIA.The arthritis index,radiologic and histologic scores were recorded to evaluate the severity change of arthritis.Serum levels of IFN-? were examined by ELISA.Results: Competitive inhibition to wild type CⅡ263-272 of the altered CⅡ263-272 peptides(APL1,APL2,APL3) was found in PBMC from RA patients.Among them,APL3 with substitution of residues 267(Q),270(K) and 271(G) to A showed the most significant effect and thus was used in the treatment of CIA rats.We observed significantly reduced arthritis scores in CIA rats treated with 100 ?g/dose of APL as compared with rats treated with PBS and peptide control.The mean radiographic and histologic scores was also markedly lower in APL-treated CIA rats than in PBS or peptide control-treated rats.On day 35 after immunization,the serum level of IFN-? in rats was examined and a significantly low level of serum IFN-? was found in APL-treated rats.Conclusion: CⅡ263-272 peptide with TCR-contact residues substitutions inhibited joint destruction in CIA rats and down-regulated IFN-? production,suggesting that altered CⅡ peptide might be potentially therapeutic in rheumatoid arthritis.
