Anti-inflammatory steroid signalling in the human peritoneum

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 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD1) enzyme, enabling intracrine generation of anti-inflammatory cortisol to minimise tissue damage. We asked if human PSE cells show an 11 beta HSD1 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). niRNA levels corresponding to the genes of interest (11 beta HSD1, 11 beta HSD2, cyclooxygenase-2, COX-2) were measured by quantitative RT-PCR. IL-1 alpha (0(.)5ng/ml) stimulated 11 beta HSD1 and COX-2 mRNA levels in PSE cells but 11 beta HSD2 was unaffected. Cortisol (1 mu M), not progesterone (1 mu M), increased 11 beta HSD1 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 11 beta HSD1 is lower in PSE and less responsive to IL-alpha. This could help explain why peritoneal healing often leads to adhesion formation, whereas postovulatory ovarian healing is scar-free.