Blockade of interleukin-17A protects against coxsackievirus B3-induced myocarditis by increasing COX-2/PGE2 production in the heart
Blockade of interleukin-17A protects against coxsackievirus B3-induced myocarditis by increasing COX-2/PGE2 production in the heart
复制标题
阻断 IL-17A 可通过增加心脏中 COX-2/PGE2 的产生来预防柯萨奇病毒 B3 诱导的心肌炎
DOI：
10.1111/j.1574-695x.2011.00918.x
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发表时间：
2012-04-01
影响因子：
--
通讯作者：
Chen, Haozhu
中科院分区：
文献类型：
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作者：
Xie, Yuquan;Chen, Ruizhen;Chen, Haozhu
Th17/白细胞介素(IL)-17轴控制炎症，可能在实验性自身免疫性心肌炎（EAM）和其他自身免疫性疾病的发病机制中起重要作用。然而，在柯萨奇病毒诱导的心肌炎中Th17细胞反应增加的机制尚不清楚。本研究旨在阐明阻断IL-17A对急性病毒性心肌炎（AVMC）小鼠的调节机制。结果显示，急性心肌炎心肌组织中IL-17A和COX-2蛋白显著升高，脾脏中Th17细胞显著升高。在病毒性心肌炎第7天使用抗小鼠IL-17Ab阻断IL-17A， AVMC小鼠与同型对照小鼠相比，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CVB3复制和心肌损伤显著减少。这些结果提示Th17/IL-17轴通过诱导COX-2和前列腺素E2与急性心肌炎病毒复制密切相关。
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.