Stimulation of prostaglandin E(2) synthesis by interleukin-1 beta is amplified by interferons but inhibited by interleukin-4 in human amnion-derived WISH cells

Human amnion-derived WISH cells synthesize little prostaglandin E(2) at the basal state. However, the cells were stimulated greatly to synthesize prostaglandin E(2) by interleukin-1 beta in a dose-dependent manner. Stimulation by interleukin-1 beta was synergistically increased by pretreatment of the cells with interferon alpha or gamma, which alone were inactive. Synergism by interferons was dose-dependent. Stimulation by interleukin-1 beta, on the contrary, was inhibited by preincubation of the cells with interleukin-4. Inhibition by interleukin-4 was also dose-dependent. Regulation of prostaglandin E(2) synthesis by cytokines was further examined at the m-RNA level of cyclooxygenase-2. Quantitative reverse transcription-polymerase chain reaction indicated that the m-RNA level was not increased by interferon-gamma but was synergistically increased by interferon-gamma plus interleukin-1 beta. Furthermore, the m-RNA level increased by interleukin-1 beta was attenuated by interleukin-4. These results indicate that regulation of interleukin-1 beta-stimulated prostaglandin E(2) synthesis by interferons and interleukin-4 is controlled at the m-RNA level of cyclooxygenase-2.