Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice.

Jing Ye,Lei Shi,Huimin Jiang,Jun Wan,Zhen Wang,Yingzhong Lin,Ling Liu,Qingwei Ji,Yao Xu,Jianfang Liu,Menglong Wang,Ying Shi,Ying Huang

doi:10.1155/2017/5635929

Abstract

Background Interleukin- (IL-) 22 is considered a proinflammatory cytokine. Recent evidence has demonstrated that it plays a role in cardiovascular diseases. In the recent study, we investigate whether IL-22 is involved in cardiac hypertrophy. Methods Angiotensin II was used to build hypertrophy model and the IL-22 and IL-22 receptor 1 (IL-22R1) levels in heart tissue were measured. In addition, angiotensin II-treated mice received an injection of anti-IL-22-neutralizing antibody (nAb) to investigate the effects of IL-22 nAb on myocardial hypertrophy, cardiac function, and cardiac fibrosis; the activation of the signaling pathway and the prohypertrophic inflammatory cytokine mRNA levels was detected. Furthermore, the effect of IL-22 nAb on angiotensin II-induced hypertrophy in vitro was also determined. Results IL-22 and IL-22R1 levels were significantly increased after angiotensin II infusion. Anti-IL-22 nAb significantly alleviated the severity of hypertrophy, prevented systolic and diastolic abnormalities, reduced cardiac fibrosis, STAT3 and ERK phosphorylation, and downregulated the mRNA expression of IL-17, IL-6, IL-1β, IFN-γ, and TNF-α. In addition, IL-22 nAb attenuated angiotensin II-induced hypertrophy in H9C2 cells. Conclusion Our data demonstrated that neutralization of IL-22 alleviated angiotensin II-induced cardiac hypertrophy. The downregulation of IL-22 may be a novel therapeutic strategy to prevent cardiac hypertrophy.

Highlights

Pathological cardiac hypertrophy, which is characterized by myocardial enlargement and abnormal fibrosis of the extracellular matrix, is a compensatory stage of chronic heart failure (CHF)
Hematoxylin and eosin (H&E) staining of heart tissue confirmed that cardiac hypertrophy induced by angiotensin II was prevented by mouse anti-IL-22 neutralizing antibody (nAb) (Figure 2(a))
We found that longer angiotensin II infusion resulted in higher levels of hypertrophy marker proteins, which represents a more serious degree of cardiac hypertrophy, with a parallel trend between the progressive increase in IL-22/IL-22 receptor 1 (IL-22R1) protein levels and the seriousness of cardiac hypertrophy

Summary

Introduction

Pathological cardiac hypertrophy, which is characterized by myocardial enlargement and abnormal fibrosis of the extracellular matrix, is a compensatory stage of chronic heart failure (CHF). Accumulating evidence has demonstrated that IL-22 has an anti-inflammatory effect and ameliorates diseases by reducing inflammation [9, 10]. This phenomenon was observed in cardiovascular diseases. Angiotensin II-treated mice received an injection of anti-IL-22-neutralizing antibody (nAb) to investigate the effects of IL-22 nAb on myocardial hypertrophy, cardiac function, and cardiac fibrosis; the activation of the signaling pathway and the prohypertrophic inflammatory cytokine mRNA levels was detected. Anti-IL-22 nAb significantly alleviated the severity of hypertrophy, prevented systolic and diastolic abnormalities, reduced cardiac fibrosis, STAT3 and ERK phosphorylation, and downregulated the mRNA expression of IL-17, IL-6, IL-1β, IFN-γ, and TNF-α. The downregulation of IL-22 may be a novel therapeutic strategy to prevent cardiac hypertrophy

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