Effect of cytokines on prostaglandin E2 and prostacyclin production in primary cultures of human myometrial cells.
The objective of this study was to characterize interleukin-1, -6, and -8 (IL-1-, IL-6-, and IL-8)-induced prostacyclin (PGI2 as 6-keto PGF1 alpha) and prostaglandin E2 (PGE2) production in primary cultures of human myometrial cells. Prostaglandins (PGs) released into the culture media were quantitated by specific radioimmunoassays. IL-1, but not IL-6 or IL-8, caused a dose- and time-dependent increase in the production of both PGI2 and PGE2. Half-maximally stimulating doses (EC50) of IL-1 were about 0.1 ng/ml, and maximal responses were observed at 1-10 ng/ml, amounting to 15- to 23-fold increases over unstimulated controls. The action of IL-1 was greatly potentiated by the protein kinase C-activating phorbol ester, TPA, and inhibited by actinomycin D and cycloheximide. IL-1-induced PG production was also suppressed by dexamethasone, by the natural IL-1 receptor antagonist (IL-1ra), and by transforming growth factor1 beta (TGF1 beta). It is concluded that IL-1 is a potent agonist of PG synthesis in human myometrial cells, acting by a mechanism dependent on the synthesis of new proteins, presumably key enzymes (phospholipase A2 and/or cyclo-oxygenase-2). This study has added further support to the notion that the myometrium serves as a target for the inflammatory cytokine, IL-1, and thereby may be affected directly, thus promoting preterm labor associated with intrauterine infection.
Todd
H M
HM
Department of Obstetrics and Gynecology, St. Louis University School of Medicine, Missouri.
Dundoo
V L
VL
Gerber
W R
WR
Cwiak
C A
CA
Baldassare
J J
JJ
Hertelendy
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000704:Analysis of Variance; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D015121:6-Ketoprostaglandin F1 alpha; D003513:Cycloheximide; D011464:Epoprostenol; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate