Open AccessInterleukin 22 Promotes Blood Pressure Elevation and Endothelial Dysfunction in Angiotensin II –Treated Mice
Author(s) -
Ye Jing,
Ji Qingwei,
Liu Jianfang,
Liu Ling,
Huang Ying,
Shi Ying,
Shi Lei,
Wang Menglong,
Liu Mengling,
Feng Ying,
Jiang Huimin,
Xu Yao,
Wang Zhen,
Song Junlong,
Lin Yingzhong,
Wan Jun
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.005875
Subject(s) - medicine , blood pressure , angiotensin ii , endothelial dysfunction , stat3 , renin–angiotensin system , endocrinology , interleukin 17 , immunology , inflammation , signal transduction , biology , biochemistry
Background CD 4+ 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. Methods and Results 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 STAT 3 (signal transducer and activator of transcription 3) pathway mediates the effect of IL ‐22 on blood pressure regulation, the special STAT 3 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. Conclusions IL ‐22 amplifies the inflammatory response, induces endothelial dysfunction and promotes blood pressure elevation in angiotensin II –induced hypertensive mice. The STAT 3 pathway mediates the effect of IL ‐22 on hypertension. Blocking IL ‐22 may be a novel therapeutic strategy to prevent and treat hypertension.