Role of endogenous TNF-α in cardiomyocyte apoptosis induced by bacteria lipoprotein and the protective effect of IL-10

Abstract

Cardiomyocyte apoptosis is thought to play an important role in sepsis-induced cardiodepression. Previous studies mainly focused on the role of exogenous TNF-α in sepsis-induced cardiac damage, however, the role of endogenous TNF-α is rarely known. Therefore, we hypothesized that endogenous TNF-α also contributed to sepsis-induced cardiomyocyte apoptosis. Primary neonatal rat cardiomyocytes were time-and dose-dependently stimulated with BLP and TNF-α. In separate experiments, cells were treated with TNF-α antagonist and IL-10, respectively, to determine effects of endogenous TNF-α and exogenous IL-10 on BLP-induced cardiomyocyte apoptosis. After treatment, apoptosis was evaluated by nuclear condensation, membrane permeability change, caspase-3 activation, and pro-to anti-apoptotic protein (bax to bcl-2) expression. Treatment of cardiomyocytes with BLP and TNF-α both significantly induced caspase-3 activation in a time-and dose-dependent manner and caused apparent nuclear condensation and increased membrane permeability. TNF-α antagonist pretreatment attenuated BLP-induced caspase-3 activation, and downregulated bax/bcl-2 ratio. In addition, administration of IL-10 inhibited TNF-α production and suppressed cardiomyocyte apoptosis induced by BLP. Our data suggest that endogenous TNF-α play an important role in BLP-induced cardiomyocyte apoptosis and IL-10 protect cardiomyocytes from BLP-induced apoptosis, an effect partially through inhibition of endogenous TNF-α production.