Cross talk of tumor necrosis factor-α and epidermal growth factor in human microvascular endothelial cells

Hiroto Izumi, Mayumi Ono, Shin Ushiro, Kimitoshi Kohno, Hsiang Fu Kung, Michihiko Kuwano

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Our previous studies imply that tumor necrosis factor-α (TNP-α) 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-α 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-α. In vitro kinase activity of EGF receptor was also enhanced by TNF-α as well as by EGF. Furthermore, expression of the c-fos gene was enhanced in response to either EGF or TNF-α. 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-α. TNF-α-induced c-fos gene expression appeared to be partly due to its transactivation of EGF receptor. EGF and TNF-α could enhance c-fos gene expression when protein kinase C was down-regulated by phorbol ester myristate (PMA). Gel retardation assay with the NF-κB consensus sequence showed that NF-κB binding activity was dramatically activated by TNF-α, but not by EGF or PMA. The binding of another transcription factor, AP-1 (Jun/Fos), was enhanced by EGF, TNF-α, and PMA, whereas TNF-α could still activate AP-1 after longer exposure to EGF. TNF-α-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.

Original languageEnglish
Pages (from-to)654-662
Number of pages9
JournalExperimental Cell Research
Issue number2
Publication statusPublished - Oct 1994

All Science Journal Classification (ASJC) codes

  • Cell Biology


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