Abstract
Background. Prostaglandin E2 (PGE2) is reportedly synthesized in the amnion, and its levels are increased during labor. Our objective was to measure the level of PGE2 induced by interleukin (IL)-1a following treatment with ceramide analogs in amnion-derived cells.
Methods. Amnion-derived (WISH) cells were cultured and stimulated by IL-1a, IL-1 receptor antagonist (ra), C2-ceramide and C6-ceramide. The levels of PGE2 in the media were measured by ELISA. The induction of prostaglandin H synthase (PGHS)-2 mRNA was detected by reverse transcription and polymerase chain reaction (RT-PCR).
Results. Following stimulation with IL-1a, the production of PGE2 could not be detected until incubation had continued for 2 h, but this production appeared to continue after4hof incubation. The production of PGE2 was significantly increased by IL-1a, and was suppressed by IL-1 ra, in a dose-dependent manner. PGE2 production was significantly increased by IL1a and C2-ceramide as compared with IL-1a alone. However, PGE2 production was not significantly increased by IL-1a and C6-ceramide as compared with IL-1a alone. PGHS-2 mRNA were induced by treatment with IL-1a, and were strongly induced by treatment with IL-1a and C2-ceramide by RT-PCR.
Conclusions. Results suggest that IL-1a induce the PGHS-2 mRNA and stimulate the production of PGE2 by a mechanism that involves the sphingomyelin-ceramide system. Ceramide may be important in increasing the production of PGE2 during parturition.