title: Anti-inflammatory steroid signalling in the human peritoneum.
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 11beta hydroxysteroid dehydrogenase type 1 (11betaHSD1) enzyme, enabling intracrine generation of anti-inflammatory cortisol to minimise tissue damage. We asked if human PSE cells show an 11betaHSD1 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-1alpha (IL-1alpha) with/without anti-inflammatory steroid (cortisol or progesterone). mRNA levels corresponding to the genes of interest (11betaHSD1, 11betaHSD2, cyclooxygenase-2, COX-2) were measured by quantitative RT-PCR. IL-1alpha (0.5 ng/ml) stimulated 11betaHSD1 and COX-2 mRNA levels in PSE cells but 11betaHSD2 was unaffected. Cortisol (1 microM), not progesterone (1 microM), increased 11betaHSD1 mRNA and synergistically enhanced IL-1alpha action. Cortisol suppressed IL-1alpha-stimulated COX-2 more effectively than progesterone. PSE cells had a significantly lower basal 11-oxoreductase enzyme activity than OSE cells; IL-1alpha 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-1alpha and anti-inflammatory steroids in qualitatively similar ways as OSE. However, the enzymatic activity of 11betaHSD1 is lower in PSE and less responsive to IL-1alpha. This could help explain why peritoneal healing often leads to adhesion formation, whereas postovulatory ovarian healing is scar-free.
authors.affiliation: University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: K S
authors.initials: KS
authors.lastname: Fegan
authors.forename: M T
authors.initials: MT
authors.lastname: Rae
authors.forename: H O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: S G
authors.initials: SG
authors.lastname: Hillier
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D004357:Drug Synergism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000494:pharmacology*; D008875:Middle Aged; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D053582:Interleukin-1alpha; D012333:RNA, Messenger; D011987:Receptors, Steroid; D013256:Steroids; D011374:Progesterone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D051546:Cyclooxygenase 2; D006854:Hydrocortisone