Anti-inflammatory steroid signalling in the human peritoneum

Fegan, K S; Rae, Mick T; Critchley, Hilary O D; Hillier, Stephen G

Abstract

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-1α (IL-1α) 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-1α (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-1α action. Cortisol suppressed IL-1α-stimulated COX-2 more effectively than progesterone. PSE cells had a significantly lower basal 11-oxoreductase enzyme activity than OSE cells; IL-1α 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-1α 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-1α. This could help explain why peritoneal healing often leads to adhesion formation, whereas postovulatory ovarian healing is scar-free.

Citation

Fegan, K. S., Rae, M. T., Critchley, H. O. D., & Hillier, S. G. (2008). Anti-inflammatory steroid signalling in the human peritoneum. Journal of Endocrinology, 196, 369-376. https://doi.org/10.1677/JOE-07-0419

• Journal Article Type: Article
• Publication Date: 2008
• Deposit Date: Mar 27, 2014
• Print ISSN: 0022-0795
• Electronic ISSN: 1479-6805
• Publisher: BioScientifica
• Peer Reviewed: Peer Reviewed
• Volume: 196
• Pages: 369-376
• DOI: https://doi.org/10.1677/JOE-07-0419
• Keywords: Peritoneal surface epithelial (PSE); ovarian; SE (OSE); inflammation-associated expression of 11b; hydroxysteroid dehydrogenase type 1 (11bHSD1) enzyme
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/6688
• Publisher URL: http://dx.doi.org/10.1677/JOE-07-0419