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

Abstract
Recombinant tumor necrosis factor (TNF), epidermal growth factor (EGF), and transforming growth factor β (TGF‐β) stimulated growth of confluent human diploid fibroblasts (FS‐4 cells) in the presence of fetal calf serum. TGF‐β synergistically enhanced both the TNF‐ and EGF‐stimulated 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‐β‐induced growth of FS‐4 cells. Mitogenic responses of indomethacin‐treated cells to EGF, TNF, and TGF‐β were similarly suppressed by the addition of exogenous prostaglandin D2 (PGD2). Other prostaglandins such as PGE2 and PGF produced less inhibition of the cell growth.

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