Cross talk of tumor necrosis factor-alpha and epidermal growth factor in human microvascular endothelial cells.
Our previous studies imply that tumor necrosis factor-alpha (TNF-alpha) and epidermal growth factor (EGF) might share a common signal transduction pathway in human omental microvascular endothelial (HOME) cells. Exposure of cultured HOME cells to TNF-alpha for 10 min enhanced EGF receptor phosphorylation at a rate comparable to EGF. Apparent phosphorylation of tyrosine residues was observed in addition to serine/threonine of the EGF receptor by EGF, but only a slightly if any tyrosine phosphorylation by TNF-alpha. In vitro kinase activity of EGF receptor was also enhanced by TNF-alpha as well as by EGF. Furthermore, expression of the c-fos gene was enhanced in response to either EGF or TNF-alpha. Pretreatment of HOME cells with EGF for 12 h almost completely blocked the induction of the c-fos gene by EGF and partially blocked the c-fos induction by TNF-alpha. TNF-alpha-induced c-fos gene expression appeared to be partly due to its transactivation of EGF receptor. EGF and TNF-alpha could enhance c-fos gene expression when protein kinase C was down-regulated by phorbol ester myristate (PMA). Gel retardation assay with the NF-kappa B consensus sequence showed that NF-kappa B binding activity was dramatically activated by TNF-alpha, but not by EGF or PMA. The binding of another transcription factor, AP-1 (Jun/Fos), was enhanced by EGF, TNF-alpha, and PMA, whereas TNF-alpha could still activate AP-1 after longer exposure to EGF. TNF-alpha-induced activation of c-fos gene appears to be mediated through pleiotropic mechanisms and partly through a common signal with EGF, possibly through EGF receptor in microvascular endothelial cells.
Izumi
H
H
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan.
Ono
M
M
Ushiro
S
S
Kohno
K
K
Kung
H F
HF
Kuwano
M
M
D001483:Base Sequence; D004730:Endothelium, Vascular / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D006801:Humans; D008833:Microcirculation / Q000166:cytology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009852:Omentum / Q000098:blood supply; D010449:Peptide Mapping; D010766:Phosphorylation; D019000:Phosphotyrosine; D011485:Protein Binding; D011493:Protein Kinase C / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D014409:Tumor Necrosis Factor-alpha; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate