Interleukin 22 Promotes Blood Pressure Elevation and Endothelial Dysfunction in Angiotensin II-Treated Mice.
Interleukin 22 Promotes Blood Pressure Elevation and Endothelial Dysfunction in Angiotensin II-Treated Mice.
复制标题
白细胞介素 22 促进血管紧张素 II 治疗小鼠的血压升高和内皮功能障碍
DOI：
10.1161/jaha.117.005875
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发表时间：
2017-10-03
影响因子：
5.4
通讯作者：
Wan J
中科院分区：
文献类型：
--
作者：
Ye J;Ji Q;Liu J;Liu L;Huang Y;Shi Y;Shi L;Wang M;Liu M;Feng Y;Jiang H;Xu Y;Wang Z;Song J;Lin Y;Wan J
CD4+辅助性T细胞(Th)包括Th1、Th2和Th17细胞，在血管紧张素II诱导的高血压中起关键作用。Th22细胞是一种新的Th细胞亚群，通过产生IL-22参与心血管疾病。本研究旨在探讨IL-22是否参与高血压的发生。血管紧张素II注射组小鼠外周血中Th22细胞和IL-22水平明显升高。为了确定Th22/IL-22在血压调节中的作用，用重组小鼠IL-22(一种抗IL-22中和单抗)或对照进行了血管紧张素II注射小鼠的治疗。重组IL-22治疗后血压升高，炎症反应增强，内皮功能障碍加重，而抗IL-22中和单抗可降低血压，减轻炎症反应，减轻内皮功能障碍。为了确定信号转导和转录激活因子3(STAT3)途径是否介导了IL-22对血压的调节作用，用重组IL-22处理小鼠，应用了STAT3途径特异性抑制剂S31-201。S31-201治疗可明显改善血压升高和内皮功能障碍所致的IL-22效应。此外，高血压病患者血清IL-22水平较正常人显著升高。相关分析显示IL-22水平与血压呈正相关。IL-22可增强血管紧张素II诱导的高血压小鼠的炎症反应，诱导血管内皮细胞功能障碍，并促进血压升高。STAT3通路介导了IL-22对高血压的作用。阻断IL-22可能是防治高血压的一种新的治疗策略。
CD4+ T helper (Th) cells, including Th1, Th2, and Th17 cells, play critical roles in angiotensin II–induced hypertension. Th22 cells, a novel subset of Th cells, take part in cardiovascular diseases by producing IL‐22 (interleukin 22). This study aimed to investigate whether IL‐22 is involved in hypertension. Th22 cells and IL‐22 levels were detected in angiotensin II–infused mice, and the results showed that Th22 cells and IL‐22 levels significantly increased. To determine the effect of Th22/IL‐22 on blood pressure regulation, angiotensin II–infused mice were treated with recombinant mouse IL‐22, an anti–IL‐22 neutralizing monoclonal antibody, or control. Treatment with recombinant IL‐22 resulted in increased blood pressure, amplified inflammatory responses, and aggravated endothelial dysfunction, whereas the anti–IL‐22 neutralizing monoclonal antibody decreased blood pressure, reduced inflammatory responses, and attenuated endothelial dysfunction. To determine whether the STAT3 (signal transducer and activator of transcription 3) pathway mediates the effect of IL‐22 on blood pressure regulation, the special STAT3 pathway inhibitor S31‐201 was administered to mice treated with recombinant IL‐22. S31‐201 treatment significantly ameliorated the IL‐22 effects of increased blood pressure and endothelial dysfunction. In addition, serum IL‐22 levels were significantly increased in hypertensive patients compared with healthy persons. Correlation analysis showed a positive correlation between IL‐22 levels and blood pressure. IL‐22 amplifies the inflammatory response, induces endothelial dysfunction and promotes blood pressure elevation in angiotensin II–induced hypertensive mice. The STAT3 pathway mediates the effect of IL‐22 on hypertension. Blocking IL‐22 may be a novel therapeutic strategy to prevent and treat hypertension.