Stimulation of prostaglandin E2 synthesis by interleukin-1/3 is amplified by interferons but inhibited by interleukin-4 in human amnion-derived WISH cells

摘要

Human amnion-derived WISH cells synthesize little prostaglandin E2 at the basal state. However, the cells were stimulated greatly to synthesize prostaglandin E2 by interleukin-1/3 in a dose-dependent manner. Stimulation by interleukin-1/3 was synergistical I y increased by pretreatment of the cells with interferon a or y, which alone were inactive. Synergism by interferons was dose-dependent. Stimulation by interleukin-1/3, on the contrary, was inhibited by preincubation of the cells with interleukin-4. Inhibition by interleukin-4- was also dose-dependent. Regulation of prostaglandin E2 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- -y but was synergistically increased by interferon-y plus interleukin-1/3. Furthermore, the m-RNA level increased by interleukin-1/3 was attenuated by inteleukin-4. These results indicate that regulation of interleukin-l/3-stimulated prostaglandin E2 synthesis by interferons and interleukin-4 is controlled at the m-RNA level of cyclooxygenase-2.