Modulation of the prostaglandin E receptor: A possible mechanism for infection-induced preterm labor

Objective: To evaluate the modulatory effects of interleukin (IL)-1 beta and prostaglandin (PG)E-2 on the PGE(2) receptor subtype EP1 in amnion cell cultures. Methods: Amnion cell cultures were incubated in increasing concentrations of (IL)-1 beta or PGE,. Cultures were also incubated in high concentrations of IL-1 beta and PGE(2) in combination. Changes in EP1 receptor levels were evaluated by western and northern blot analysis. Culture fluid PGE(2) levels were measured by enzyme-linked immunosorbent assay. Results: EP1 receptor protein levels decreased with increasing levels of PGE(2) (v = -0.82, P < .05). EP1 receptor protein (r = 0.95, P < .05), EP1 mRNA (v = 0.95, P < .01), and culture fluid PGE(2) levels (P < .01) were all increased after IL-1 beta administration. EP1 receptor levels also increased approximately fourfold in response to IL-1 beta incubation even in the presence of high agonist (PGE(2)) concentrations (P < .01). Conclusion: The results of this study show that IL-1 beta might be involved in infection-induced preterm labor by interfering with the normal regulation of EP1 receptor levels and with the promotion of increased PGE(2) production in amnion tissue. (C) 1999 by The American College of Obstetricians and Gynecologists.