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

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.

Interleukin‑22 is elevated in the atrium and plasma of patients with atrial fibrillation and increases collagen synthesis in transforming growth factor‑β1‑treated cardiac fibroblasts via the JNK pathway

“…IL-22 is an immune-related cytokine secreted primarily by macrophages and CD4 + T lymphocytes. An increasing number of studies have reported that IL-22 expression is increased in inflammation-mediated cardiovascular disease (16)(17)(18)(19)(20)(21). Previous studies reported that both T helper (Th) 22 and IL-22 levels were increased in Coxsackie virus B3-induced acute and chronic viral myocarditis and dilated cardiomyopathy (26,27).…”

“…no. AF-100-21M-2; PeproTech, Inc.) (17,26,27), and saline treatment as control. Following treatment at 37˚C for 12 h, fibrosis expression in cardiac fibroblasts was detected.…”

“…It is involved in a variety of biological processes, including inflammatory reactions, oxidative stress, apoptosis, autophagy, cell migration and endothelial dysfunction (12)(13)(14)(15)(16). Previous studies revealed that IL-22 regulates the progression of a variety of cardiovascular diseases, including hypertension, cardiac fibrosis, aortic dissection, atherosclerosis and viral myocarditis (16)(17)(18)(19)(20)(21). However, the expression of IL-22 in patients with AF is yet to be elucidated.…”

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

“…IL-17 seems to have dose-and cell source-dependent inflammatory and pro-fibrotic effect, whereas interleukin 22 (IL-22) was associated with protecting against liver fibrosis through downregulation of the TGF-b1/Notch signaling pathway [194] but being pro-fibrotic in cardiac fibrosis through STAT3/and ERK and IL-17, IL-6, IL-1b, IFN-g, and TNF-a [195] and pro-atherosclerotic [196]. Both, IL-17 and IL-22 are associated with poor prognosis in liver cancer [197], but the exact roles of IL-17 and IL-22 need to be defined in detail in regard to concentration, kind of inflammation, and period of chronic inflammation involved in signaling axis and cell sources.…”

Erratum to “Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice”

“…In the article “Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice” [ 1 ], there was an error in Figure 1(a) , where the IL-22, β -MHC, and GAPDH bands were triplicated, due to a production error. The corrected figure is shown below.…”