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BOR - Papers in Press, published online ahead of print April 2, 2003.
Biol Reprod 2003, 10.1095/biolreprod.102.013698
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BIOLOGY OF REPRODUCTION 69, 331–337 (2003)
DOI: 10.1095/biolreprod.102.013698
© 2003 by the Society for the Study of Reproduction, Inc.


Pregnancy

Progesterone Represses Interleukin-8 and Cyclo-Oxygenase-2 in Human Lower Segment Fibroblast Cells and Amnion Epithelial Cells1

Jenifer A.Z. Loudon2, Catherine L. Elliott, Frank Hills, and Phillip R. Bennett

Imperial College Parturition Research Group, Wolfson and Weston Centre for Family Health, Institute of Reproductive and Developmental Biology, London W12 0HN, United Kingdom

Labor is preceded by cervical ripening through upregulation of interleukin (IL)-1ß, 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-1ß 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-1ß 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-1ß 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-1ß increased IL-8 and PGE2 synthesis and COX-2 expression, but progesterone did not attenuate the effect of IL-1ß 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.

1 This study was sponsored by Tommy's, the baby's charity, and by Action Research.

2 Correspondence: Jenifer A.Z. Loudon, Imperial College Parturition Research Group, Wolfson and Weston Centre for Family Health, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Site, Du Cane Road, East Acton, London W12 0HN, United Kingdom. FAX: 44 20 7594 2189; j.loudon{at}ic.ac.uk




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