Expression of IL-23/Th17 pathway in a murine model of Coxsackie virus B3-induced viral myocarditis.
Expression of IL-23/Th17 pathway in a murine model of Coxsackie virus B3-induced viral myocarditis.
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DOI：
10.1186/1743-422x-8-301
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发表时间：
2011-06-14
期刊：
影响因子：
4.8
通讯作者：
Huang YL
中科院分区：
文献类型：
--
作者：
Yang F;Wu WF;Yan YL;Pang Y;Kong Q;Huang YL
IL-23/Th17 通路与许多慢性炎症和自身免疫性疾病的发病机制有关。它是否调节病毒性心肌炎（VMC）尚不清楚。为了研究 IL-23/Th17 轴在 VMC 中的发病机制，我们使用雄性 BALB/c 小鼠通过柯萨奇病毒 B3 (CVB3) 腹腔注射诱导 VMC。通过半定量 RT-PCR 评估 VMC 小鼠心肌中的 IL-23、IL-17 以及信号转导子和转录激活子 3 (STAT3) mRNA。通过 ELISA 评估血清中的 IL-23 和 IL-17 蛋白。通过免疫组织化学染色评估心肌中磷酸化 STAT3 (p-STAT3) 蛋白的表达。使用流式细胞术分析评估 Th17 亚群的频率。将 VMC 小鼠分离的 CD4+ T 细胞与重组 IL-23(rIL-23) 进行体外培养。此外，使用 STAT3 特异性抑制剂 (S3I-201) 来测试 STAT3 的调节是否可能是 Th17 减少的部分原因。结果显示VMC小鼠IL-23、IL-17、STAT3 mRNA和蛋白表达增加。当来自 VMC 小鼠的纯化 CD4+ T 细胞与 rIL-23 一起体外培养时，Th17 细胞的频率显着增加，同时培养的 CD4+ T 细胞上清液中 IL-17 的产生也显着增加。 S3I-201显着抑制Th17细胞增殖。 IL-23/Th17 通路轴在小鼠 VMC 中强烈表达，确定了一条在病毒性心肌炎中具有潜在意义的新通路。
The IL-23/Th17 pathway is implicated in the pathogenesis of a number of chronic inflammatory and autoimmune diseases. Whether it regulates the viral myocarditis (VMC) is unknown. To examine the pathogenesis role of IL-23/Th17 axis in VMC, we used male BALB/c mice to induced VMC by Coxsackie virus B3 (CVB3) peritoneal injection. IL-23, IL-17, and signal transducer and activator of transcription 3 (STAT3) mRNA in the myocardium of VMC mice were assessed by semi-quantitative RT-PCR. IL-23 and IL-17 protein from blood serum were evaluated by ELISA. Phosphorylated-STAT3 (p-STAT3) protein expression in the myocardium was evaluated by immunohistochemical staining. Flow cytometric analysis was used to evaluate the frequencies of Th17 subsets. Isolated CD4+ T cells from VMC mice were cultured with recombinant IL-23(rIL-23) in vitro. In addition, a STAT3-specific inhibitor (S3I-201) was used to test whether regulation of STAT3 could be partly responsible for Th17 diminution. Results showed that expression of IL-23, IL-17, STAT3 mRNA and protein increased in VMC mice. When purified CD4+ T cells derived from VMC mice were cultured in vitro with rIL-23, the frequency of Th17 cells was dramatically increased, accompanied by significantly enhanced production of IL-17 in the supernatants of cultured CD4+ T cells. S3I-201 significantly restrained Th17 cell proliferation. The IL-23/Th17 pathway axis is strongly expressed in murine VMC, identifying a novel pathway of potential significance in viral myocarditis.