Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation

Background: We have already reported that TNF-alpha increases cardiomyocyte apoptosis and IL-10 treatment prevented these effects of TNF-alpha. Present study investigates the role of Akt and Jak/Stat pathway in the IL-10 modulation of TNF-alpha induced cardiomyocyte apoptosis. Methodology/Principal findings: Cardiomyocytes isolated from adult Sprague Dawley rats were exposed to TNF-alpha (10 ng/ml), IL-10 (10 ng/ml) and TNF-alpha+IL-10 (ratio 1) for 4 h. Exposure to TNF-alpha resulted in an increase in cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay. IL-10 by itself had no effect, but it prevented TNF-alpha induced apoptosis. IL-10 treatment increased Akt levels within cardiomyocytes and this change was associated with an increase in Jak1 and Stat3 phosphorylation. Pre-exposure of cells to Akt inhibitor prevented IL-10 induced Stat3 phosphorylation. Furthermore, in the presence of Akt or Stat3 inhibitor, IL-10 treatment was unable to block TNF-alpha induced cardiomyocyte apoptosis. Conclusion: It is suggested that IL-10 modulation of TNF-alpha induced cardiomyocyte apoptosis is mediated by Akt via Stat3 activation.