Alteration of IL-17 related protein expressions in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer
Alteration of IL-17 related protein expressions in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer
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DOI：
10.1253/circj.72.813
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发表时间：
2008-05-01
影响因子：
3.3
通讯作者：
Aizawa, Yoshifusa
中科院分区：
文献类型：
--
作者：
Chang, He;Hanawa, Haruo;Aizawa, Yoshifusa
研究背景辅助性T细胞（Th 1）/Th 2细胞因子平衡在心肌炎的发病机制中起重要作用。近年来，一些研究表明白细胞介素（IL）-17（IL-17）是一种T细胞（Th 17）源性的促炎细胞因子，是炎症和自身免疫性疾病中组织炎症的主要介质。实验性自身免疫性心肌炎（EAM）是一种T细胞介导的自身免疫性疾病;然而，IL-17在大鼠EAM发展中的致病作用在很大程度上仍然未知。方法和结果在本研究中，研究IL-17相关蛋白表达的变化，然后观察基于流体动力学的递送编码IL-10-IG基因的质粒DNA对大鼠EAM的影响以及IL-10-Ig基因对大鼠EAM的影响。评价IG对IL-17的影响。结果表明，IL-17在aT细胞中的表达高于IFN-γ，且IL-17相关蛋白在心肌中的表达高峰出现在EAM的早期。此外，我们观察到IL-10-IG基因治疗在控制EAM中是有效的，并且IL-10-IG显著抑制IL-17以及其他促炎细胞因子IL-1 β和TNF-α的表达，结论在EAM大鼠心脏早期，α β T细胞大量分泌IL-17，IL-17在EAM大鼠心脏早期表达，IL-17在EAM大鼠心脏早期表达，IL-17在EAM大鼠心脏早期表达，IL-17在EAM大鼠心脏早期表达。17抑制可能是IL-10-IG治疗EAM的一个可能机制。提示Th 17产生的IL-17在大鼠EAM的发病机制中起重要作用。
Background T-helper (Th)1/Th2 cytokine balance plays an important role in the pathogenesis of myocarditis. Recently, some studies indicate that interleukin (IL)-17, known as a T cell (Th17)-derived proinflammatory cytokine, is the major mediator of tissue inflammation in inflammatory and autoimmune diseases. Experimental autoimmune myocarditis (EAM) is a T cell-mediated autoimmune disease; however, the pathogenic role of IL-17 in the development of rat EAM remains largely unknown.Methods and Results In the present study, alterations of IL-17-related protein expressions were investigated and then the effect of hydrodynamic-based delivery of plasmid DNA encoding the IL-10-Ig gene on rat EAM and the effect of IL-10-Ig on IL-17 was evaluated. The results showed that IL-17 was expressed more highly than IFN-gamma expressed by Th1 cells in a T cells and the peaks of IL-17 related protein expression in the heart were the early phase of EAM. Moreover, we observed that IL-10-Ig gene therapy was effective in controlling EAM and that IL-10-Ig significantly suppressed the expression of IL-17 as well as other proinflammatory cytokines, IL-1 beta and TNF-alpha, in IL-1-stimulated splenocytes cultured from EAM rats.Conclusions IL-17 is highly produced by alpha beta T cells in the early phase of EAM hearts and IL-17 inhibition might be a possible mechanism of the amelioration of EAM by IL-10-Ig treatment. These data suggest that IL-17 produced by Th17 plays an important role in the pathogenesis of rat EAM.