Possible role of prostaglandins as negative regulators in growth stimulation by tumor necrosis factor and epidermal growth factor in human fibroblasts

✍ Scribed by Takamitsu Hori; Satoshi Kashiyama; Makio Hayakawa; Sayumi Shibamoto; Masafumi Tsujimoto; Naoto Oku; Fumiaki Ito

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 584 KB
• Volume: 141
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041410207

✦ Synopsis

Recombinant tumor necrosis factor (TNF), epidermal growth factor (EGF), and transforming growth factor P (TGF-P) stimulated growth of confluent human diploid fibroblasts (FS-4 cells) in the presence of fetal calf serum. TGF-P synergistically enhanced both the I N t -and ECktimulated cell growth, whereas synergism between the mitogenic action of EGF and that of TNF was not observed.

When indomethacin or acetylsalicylic acid, an inhibitor of prostaglandin production, was added to FS-4 cells, cell growth stimulated by EGF or TNF was increased, suggesting that prostaglandins induced by these mitogens antagonize their growth stimulatory actions. In contrast, neither indomethacin nor acetylsalicylic acid had a significant effect on the TGF-P-induced growth of FS-4 cells. Mitogenic responses of indomethacin-treated cells to EGF, TNF, and TGF-P were similarly suppressed by the addition of exogenous prostagldndin D2 (PGD2). Other prostaglandins such as PGE2 and PGFZa produced less inhibition of the cell growth.