The Effects And Mechanism Of The IL-1R?/IL-1RACP Heterodimer On Rat Autoimmune Myocarditis

Purpose:Estimate the effect and mechanism of IL-1R?/IL-1RAcp heterodimer on experimental autoimmune myocarditis(EAM).Methods:In vivo,all rats were immunized on day 0 and injected with the recombinant plasmid pCAGGS-IL-1R? and IL-1RAcp-Ig on day 6.Plasma was collected day 7?day 12?day17.All rats were sacrificed on day 17,and the effect of treatment was examined.The evaluation indictors including the heart weight/body weight radio,histopathology,cardiac function indexs and the expression of inflammatory cytokines.In vitro,in cos7 cells,we identificated the formation and the combining sites of the IL-1R?/IL-1RACP heterodimer with Co-Ip.In H9C2 cells and VSMC cells we evaluate the effect of the IL-1R?/IL-1RACP heterodimer on proinflammatory factors expression with real-time quantitative PCRand ELISA.Results:In vivo,compared with IL-1R? alone group,the IL-1R?/IL-1RAcp-Ig gene therapy group was more effective in controlling EAM,as indicated by a decreased HW/BW,reduced expression of BNP?inflammatory cytokines.recovered cardiac function.In vitro,we identificated the formation of the IL-1R?/IL-1RAcp heterodimer and the combining sites of the heterodimer is at the second functional domin of IL-1R?.Compared with IL-1R? alone group,IL-1R?/IL-1RAcp heterodimer significantly inhibited the inflammatory cytokines,MCP-1?IL-6?TNF-??TGF-? and IL-17 expression.Conclusion:IL-1R? and IL-1RACP can formation the heterodimer and the combining sites of the heterodimer is at the second functional domain of IL-1R?.The heterodimer can significantly alleviate myocarditis,and improve cardiac function.This will provide new therapeutic targets of myocarditis.