TNF-alpha induces interleukin-8 and endothelin-1 expression in human endothelial cells with different redox pathways.
We investigated the effect of TNF-alpha 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-alpha. By Northern blot analysis, TNF-alpha 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 (H(2)O(2)) significantly enhanced TNF-alpha-induced IL-8 mRNA expression. Furthermore, HMECs treated with TNF-alpha 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 H(2)O(2) significantly inhibited TNF-alpha-induced ET-1 mRNA expression. Thus, TNF-alpha significantly induces both IL-8 and ET-1 gene expression in HMECs possibly through different redox signaling pathways. H(2)O(2) enhances TNF-alpha-induced IL-8 expression, but inhibits TNF-alpha-induced ET-1 expression.
Zhao
Ruo-Zhi
RZ
Diabetes Research Group, University of Manitoba, Winnipeg, Man., Canada R3E 3P4.
Chen
Xilin
X
Yao
Qizhi
Q
Chen
Changyi
C
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics*; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D019332:Endothelin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase