Alteration of IL-17 related protein expressions in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer

作者：Chang He; Hanawa Haruo^*; Yoshida Tsuyoshi; Hayashi Manabu; Liu Hui; Ding Limin; Otaki Keita; Hao Kazuhisa; Yoshida Kaori; Kato Kiminori; Toba Ken; Kodama Makoto; Maruyama Hiroki; Miyazaki Junichi; Aizawa Yoshifusa

来源：Circulation Journal, 2008, 72(5): 813-819.

DOI：10.1253/circj.72.813

• cardiomyopathy
• gene therapy
• interleukin-17
• Th17
• Th1/Th2 balance

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.

• 出版日期2008-5