Stimulation of prostaglandin E2 synthesis by interleukin-1beta is amplified by interferons but inhibited by interleukin-4 in human amnion-derived WISH cells.
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-1beta in a dose-dependent manner. Stimulation by interleukin-1beta 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-1beta, 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-gamma but was synergistically increased by interferon-gamma plus interleukin-1beta. Furthermore, the m-RNA level increased by interleukin-1beta was attenuated by interleukin-4. These results indicate that regulation of interleukin-1beta-stimulated prostaglandin E2 synthesis by interferons and interleukin-4 is controlled at the m-RNA level of cyclooxygenase-2.
Harding
L
L
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Wang
Z
Z
Tai
H H
HH
D000650:Amnion / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D007372:Interferons; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone