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Journal of Endocrinology (2008) 196, 369-376       DOI: 10.1677/JOE-07-0419
© 2008 Society for Endocrinology
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Anti-inflammatory steroid signalling in the human peritoneum

K S Fegan, M T Rae1, H O D Critchley1 and S G Hillier1

University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, UK1 Queen's Medical Research Institute, Centre for Reproductive Biology, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

(Correspondence should be addressed to S G Hillier; Email: s.hillier{at}ed.ac.uk)

(M T Rae is now at School of Life Sciences, Napier University, Craiglockhart Campus, Edinburgh EH14 1DJ, UK)

Peritoneal surface epithelial (PSE) cells participate in adhesion formation following inflammatory injury yet adjacent ovarian SE (OSE) cells regenerate without scarification after ovulation. OSE cells show inflammation-associated expression of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme, enabling intracrine generation of anti-inflammatory cortisol to minimise tissue damage. We asked if human PSE cells show an 11βHSD1 response to pro-/anti-inflammatory stimulation and if so, how the 11-oxoreductase activity generated compares with OSE. PSE collected from premenopausal women undergoing surgery for benign gynaecological conditions were used to establish primary PSE cell cultures that were treated for 48 h with interleukin-1{alpha} (IL-1{alpha}) with/without anti-inflammatory steroid (cortisol or progesterone). mRNA levels corresponding to the genes of interest (11βHSD1, 11βHSD2, cyclooxygenase-2, COX-2) were measured by quantitative RT-PCR. IL-1{alpha} (0.5 ng/ml) stimulated 11βHSD1 and COX-2 mRNA levels in PSE cells but 11βHSD2 was unaffected. Cortisol (1 µM), not progesterone (1 µM), increased 11βHSD1 mRNA and synergistically enhanced IL-1{alpha} action. Cortisol suppressed IL-1{alpha}-stimulated COX-2 more effectively than progesterone. PSE cells had a significantly lower basal 11-oxoreductase enzyme activity than OSE cells; IL-1{alpha} did not significantly increase the 11-oxoreductase activity in PSE cells but did so in OSE cells. We conclude that PSE cells respond to IL-1{alpha} and anti-inflammatory steroids in qualitatively similar ways as OSE. However, the enzymatic activity of 11βHSD1 is lower in PSE and less responsive to IL-1{alpha}. This could help explain why peritoneal healing often leads to adhesion formation, whereas postovulatory ovarian healing is scar-free.




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H.-Y. Lee, T. J. Acosta, D. J. Skarzynski, and K. Okuda
Prostaglandin F2alpha Stimulates 11Beta-Hydroxysteroid Dehydrogenase 1 Enzyme Bioactivity and Protein Expression in Bovine Endometrial Stromal Cells
Biol Reprod, April 1, 2009; 80(4): 657 - 664.
[Abstract] [Full Text] [PDF]




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