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

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