TNF-α induces interleukin-8 and endothelin-1 expression in human endothelial cells with different redox pathways

We investigated the effect of TNF-α on interleukin-8 (IL-8) and endothelin-1 (ET-1) expression, and their different signal transduction pathways. Human dermal microvascular endothelial cells (HMECs) were treated with TNF-α. By Northern blot analysis, TNF-α at 50, 100, 200, and 400 U/ml significantly induced IL-8 mRNA expression by 206%, 252%, 211%, and 158%, respectively, as compared to controls (p < 0.05). Overexpression of human superoxide dismutase (SOD) by adenovirus-mediated gene transfer or addition of exogenous hydrogen peroxide (H2O2) significantly enhanced TNF-α-induced IL-8 mRNA expression. Furthermore, HMECs treated with TNF-α at 50, 100, and 200 U/ml significantly increased ET-1 mRNA expression by 71%, 82%, and 66%, respectively (p < 0.05). By contrast, SOD gene transfer and exogenous H2O2 significantly inhibited TNF-α-induced ET-1 mRNA expression. Thus, TNF-α significantly induces both IL-8 and ET-1 gene expression in HMECs possibly through different redox signaling pathways. H2O2 enhances TNF-α-induced IL-8 expression, but inhibits TNF-α-induced ET-1 expression.