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

Abstract

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-1β in a dose-dependent manner. Stimulation by interleukin-1β was synergistically increased by pretreatment of the cells with interferon α or γ, which alone were inactive. Synergism by interferons was dose-dependent. Stimulation by interleukin-1β, 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-γ but was synergistically increased by interferon-γ plus interleukin-1β. Furthermore, the m-RNA level increased by interleukin-1β was attenuated by inteleukin-4. These results indicate that regulation of interleukin-1β-stimulated prostaglandin E 2 synthesis by interferons and interleukin-4 is controlled at the m-RNA level of cyclooxygenase-2.