Epidermal growth factor and transforming growth factor-alpha enhance the interleukin-1- and tumor necrosis factor-stimulated prostaglandin E2 production and the interleukin-1 specific binding on amnion cells.

Interleukin-1 (IL-1), tumor necrosis factor (TNF), epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha) stimulate prostaglandin E2 (PGE2) production by amnion cells whereas TGF-beta inhibits the PGE2 production. During labor occurring in the setting of infection, several of these cytokines may be simultaneously present in amniotic fluid. The aim of the present study was to examine whether these cytokines modify each others' effects on amnion cell PGE2 production. Amnion cells in monolayer culture were treated with IL-1, TNF, EGF, TGF-alpha, TGF-beta 1, their combination, or vehicle. The PGE2 production and the specific binding of radiolabeled IL-1 beta on the cells were measured. IL-1 or TNF in combination with EGF or TGF-alpha stimulated synergistically the production of PGE2 by amnion cells. TGF-beta 1 did not modify the PGE2-stimulatory effect of EGF/TGF-alpha. Untreated amnion cells expressed 1030 +/- 100 IL-1 beta receptors per cell with a binding affinity of 1.40 +/- 0.26 nM. Treatment with TGF-alpha increased the number of receptors to 3940 +/- 260 per cell with no change in binding affinity. The potentiation of the PGE2-stimulatory effect of IL-1 by TGF-alpha may be related to its ability to induce IL-1 receptors on amnion cells. The synergistic effects of cytokines on amnion cell PGE2 production may promote labor.