Progesterone represses interleukin-8 and cyclo-oxygenase-2 in human lower segment fibroblast cells and amnion epithelial cells.
Labor is preceded by cervical ripening through upregulation of interleukin (IL)-1beta, IL-8, and increased prostaglandin synthesis via inducible type 2 cyclooxygenase (COX-2). Progesterone maintains myometrial quiescence during pregnancy. In this study, we examined the effects of IL-1beta and progesterone on IL-8 and prostaglandin E2 (PGE2) synthesis and IL-8 and COX-2 mRNA and promoter activity in amnion cells and lower segment fibroblast (LSF) cells. In both cell types, progesterone had no effect on basal IL-8 or PGE2 synthesis. In LSF cells, IL-1beta significantly increased IL-8 and PGE2 synthesis and COX-2 and IL-8 mRNA expression, but progesterone significantly attenuated these effects. In prelabor amnion cells, IL-1beta also increased IL-8 and PGE2 synthesis and both COX-2 and IL-8 mRNA and promoter expression; however, progesterone significantly attenuated these effects on IL-8 and PGE2 synthesis and COX-2 expression. In postlabor amnion cells, IL-1beta increased IL-8 and PGE2 synthesis and COX-2 expression, but progesterone did not attenuate the effect of IL-1beta upon IL-8 synthesis. Progesterone repression of IL-8 and COX-2 in LSF cells suggests that IL-8 and COX-2 have similar regulatory mechanisms in LSF cells and that progesterone may play a role in maintenance of cervical competence. The lack of effect of progesterone on IL-8 in postlabor cells may be the result of downregulation of the progesterone receptor during labor.
Loudon
Jenifer A Z
JA
Imperial College Parturition Research Group, Wolfson and Weston Centre for Family Health, Institute of Reproductive and Developmental Biology, London W12 0HN, United Kingdom. j.loudon@ic.ac.uk
Elliott
Catherine L
CL
Hills
Frank
F
Bennett
Phillip R
PR
D000650:Amnion / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007743:Labor, Obstetric / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007375:Interleukin-1; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D011374:Progesterone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone