Resveratrol suppresses interleukin‐6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts

• Published in: Journal of cellular physiology Vol. 235; no. 10; pp. 6969 - 6977
• Main Authors: Akhondzadeh, Fariba, Astani, Akram, Najjari, Razieh, Samadi, Morteza, Rezvani, Mohammad Ebrahim, Zare, Fatemeh, Ranjbar, Ali Mohammad, Safari, Fatemeh
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2020
• Subjects: Activation; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Animals; cardiac hypertrophy; Cardiomegaly - drug therapy; Cardiomegaly - metabolism; Cell size; Cell Survival - drug effects; Cell viability; Cells, Cultured; Cytokines; Gene expression; Gene Expression - drug effects; Glycoprotein gp130; H9c2, Resveratrol; Histone deacetylase; Hypertrophy; IL‐6; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin-6 - metabolism; Interleukins; Myocytes, Cardiac; Pathogenesis; Polymerase chain reaction; Proteins; Rats; Resveratrol; Resveratrol - pharmacology; RNA, Messenger - metabolism; SIRT1 protein; Sirtuin 1 - metabolism; Transcription; Transcription, Genetic - drug effects; H9c2, Resveratrol; cardiac hypertrophy; angiotensin II; IL-6
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29592

Inflammatory cytokine, interleukin‐6 (IL‐6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL‐6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 μM) of resveratrol (R). Cell viability was measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real‐time polymerase chain reaction technique. Enzyme‐linked immunosorbent assay was used to measure IL‐6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 μM of resveratrol were used to to evaluate its anti‐inflammatory effects. The results revealed that Ang II upregulated IL‐6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 μM) decreased IL‐6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX‐527, the response of resveratrol was partially reversed. Transcription levels of IL‐6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II‐induced hypertrophy by suppression of IL‐6 through SIRT1 activation. We investigated the effect of resveratrol on interleukin‐6 (IL‐6) expression in the absence and presence of sirtuin 1 (SIRT1) inhibitor. Based on the data reported in present study, resveratrol protects H9c2 cells against angiotensin II‐induced hypertrophy by suppression of IL‐6 through SIRT1 activation.