Regulation of interleukin-1alpha and tumor necrosis factor-alpha-induced interleukin-8 production by amnion-derived (WISH) cells.

PURPOSE OF INVESTIGATION: It has been reported that interleukin (IL)-8 is produced in the amnion and that its production is enhanced by the initiation of labor. The purpose of this study was to clarify the mechanism of IL-8 production by amnion-derived (WISH) cells. METHODS: Cells were cultured and treated with various concentrations of interleukin (IL)-1alpha, IL-1 receptor antagonist (ra), tumor necrosis factor (TNF)- alpha, C2-, C6-ceramide, mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor (U0126) and pyridinyl imidazole (p38 MAP kinase inhibitor, SB203580). IL-8 in the culture medium was measured by ELISA. RESULTS: The production of IL-8 was significantly increased by IL-1alpha or TNF-alpha, and the increase of IL-8 stimulated by IL-1alpha was suppressed by IL-1 ra in a dose-dependent manner. The increase in IL-8 production by IL-1alpha or TNF-alpha was further enhanced by simultaneous addition of C2-ceramide. The increase of IL-8 stimulated by IL-1alpha or TNF-alpha was also suppressed by treatment with U0126 or SB203580. The results of this study demonstrate that the production of IL-8 induced by IL-1alpha and TNF-alpha is enhanced by C2-ceramide, and suppressed by MEK inhibitor or P38 MAP kinase inhibitor. CONCLUSION: The results suggest that ceramide-mediated accumulation and MAP kinase-mediated suppression of inflammatory events in the amnion may play an important role in the maintenance of pregnancy and initiation of labor.