Interleukin-1 binding and prostaglandin E2 synthesis by amnion cells in culture: regulation by tumor necrosis factor-alpha, transforming growth factor-beta, and interleukin-1 receptor antagonist.

Proinflammatory cytokines may promote preterm labor in the setting of intrauterine infection. Tumor necrosis factor (TNF) and interleukin-1 (IL-1) synergistically stimulate the production of prostaglandin E2 (PGE2) by amnion cells. Transforming growth factor-beta (TGF-beta) inhibits the cytokine-stimulated PGE2 production. In the present study, we investigated the binding of IL-1 beta on human amnion cells in culture. Untreated amnion cells possessed 540 +/- 60 IL-1 receptors per cell, with a dissociation constant of 1.4 +/- 0.4 nM. Cells treated with TGF-beta 1 (10 ng/ml) had 570 +/- 110 receptors per cell. TNF-alpha (50 ng/ml) increased the number of IL-1 receptors to 2930 +/- 590. TGF-beta 1 inhibited the receptor upregulation by TNF-alpha. Cells treated with TGF-beta 1 and TNF-alpha expressed 1140 +/- 590 receptors per cell. The binding affinity was not changed by the cytokines. IL-1 receptor antagonist (IL-1ra) inhibited the stimulation of amnion cell PGE2 production by IL-1 beta, but not by TNF-alpha. Amnion cells secreted large amounts of IL-1ra (1.1 +/- 0.3 ng/10(5) cells). Treatment of the cells with TGF-beta 1 or TNF-alpha did not affect the release of IL-1ra. We conclude that IL-1 receptor expression is an important step in the regulation of the effects of cytokines on amnion cell PGE2 production.