Xie Yuquan, Chen Ruizhen, Zhang Xian, Yu Yong, Yang Yingzhen, Zou Yunzeng, Ge Junbo, Chen Haozhu, Garzino-Demo Alfredo
Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
FEMS Immunol Med Microbiol. 2012 Apr;64(3):343-51. doi: 10.1111/j.1574-695X.2011.00918.x. Epub 2011 Dec 22.
The Th17/interleukin (IL)-17 axis controls inflammation and might be important in the pathogenesis of experimental autoimmune myocarditis (EAM) and other autoimmune diseases. However, the mechanism underlying the increased Th17 cell response in coxsackievirus-induced myocarditis remains unclear. This study aimed to elucidate the regulatory mechanisms affected by blocking IL-17A responses in acute virus-induced myocarditis (AVMC) mice. The results showed that IL-17A and COX-2 proteins were significantly increased in the cardiac tissue of acute myocarditis, as were Th17 cells in the spleen. Using anti-mouse IL-17Ab to block IL-17A on day 7 of the viral myocarditis led to decreased expressions of cardiac tumor-necrosis factor alpha, IL-17A and transforming growth factor beta in AVMC mice compared to isotype control mice. COX-2 and prostaglandin E2 proteins were dramatically elevated, followed by marked reductions in CVB3 replication and myocardial injury. These results hint that the Th17/IL-17 axis is intimately associated with viral replication in acute myocarditis via induction of COX-2 and prostaglandin E2.
Th17/白细胞介素（IL）-17轴控制炎症反应，可能在实验性自身免疫性心肌炎（EAM）及其他自身免疫性疾病的发病机制中起重要作用。然而，柯萨奇病毒诱导的心肌炎中Th17细胞反应增强的潜在机制仍不清楚。本研究旨在阐明在急性病毒诱导的心肌炎（AVMC）小鼠中阻断IL-17A反应所影响的调控机制。结果显示，急性心肌炎心脏组织中IL-17A和COX-2蛋白显著增加，脾脏中的Th17细胞也增多。在病毒性心肌炎第7天使用抗小鼠IL-17Ab阻断IL-17A，与同型对照小鼠相比，AVMC小鼠心脏肿瘤坏死因子α、IL-17A和转化生长因子β的表达降低。COX-2和前列腺素E2蛋白显著升高，随后柯萨奇病毒B3（CVB3）复制及心肌损伤明显减轻。这些结果提示，Th17/IL-17轴通过诱导COX-2和前列腺素E2与急性心肌炎中的病毒复制密切相关。
