Interleukin-1 stimulates human uterine prostaglandin production through induction of cyclooxygenase-2 expression.
OBJECTIVE
Uterine infection occurs in as much as 20% of preterm labor and results in increased decidual cytokines. The objective of this study was to examine the effect of interleukin-1 (IL-1) and the cyclooxygenase-2 (COX-2) inhibitor, NS-398, on myometrial prostaglandin (PG) production and COX-2 expression.


METHODS
Human uterine myocytes were stimulated with IL-1 (0-50 ng/mL) over 24 hr. PGE2, PGF2alpha, and 6-keto F1alpha were measured by enzyme-linked immunosorbent assay. Both COX-1 and COX-2 proteins and mRNA were measured by western and northern blot, respectively.


RESULTS
IL-1 increased PG production beginning at 6 hr, COX-2 protein increased beginning at 4 hr and continued to increase at 24 hr. COX-2 mRNA increased at 2 hr and peaked at 4 hr. NS-398 blocked PG production but had no effect on COX-2 protein or mRNA.


CONCLUSIONS
IL-1 increases PG production by myometrium by increased COX-2 expression. NS-398 completely blocks IL-1-induced PG production. With intrauterine infection, IL-1 may induce labor through the autocrine production of uterotonic PGs.
Rauk
P N
PN
Magee-Womens Research Institute and the Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, PA 15213, USA. rsipnr@mail.magee.edu
Chiao
J P
JP
D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000276:immunology; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins; D009215:Myometrium / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D015237:Dinoprost; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone