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Anti-inflammatory steroid signalling in the human peritoneum
K S Fegan1, M T Rae, H O D Critchley
1University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, UK.
Peritoneal surface epithelial cells exhibit a lower 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) enzyme activity compared to ovarian surface epithelial cells. This reduced activity may explain why peritoneal healing often results in scar tissue formation.
Area of Science:
- Cell biology
- Reproductive medicine
- Inflammation research
Background:
- Peritoneal surface epithelial (PSE) cells are involved in adhesion formation after injury.
- Ovarian surface epithelial (OSE) cells regenerate without scarring post-ovulation.
- OSE cells express 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) for anti-inflammatory cortisol generation.
Purpose of the Study:
- To investigate if human PSE cells exhibit an 11betaHSD1 response to inflammatory and anti-inflammatory stimuli.
- To compare the 11-oxoreductase activity in PSE cells with that of OSE cells.
Main Methods:
- Primary human PSE cell cultures were established.
- Cells were treated with interleukin-1alpha (IL-1alpha) and anti-inflammatory steroids (cortisol or progesterone).
- Gene expression (11betaHSD1, 11betaHSD2, COX-2) and enzyme activity were measured.
Main Results:
- IL-1alpha stimulated 11betaHSD1 and COX-2 mRNA in PSE cells; 11betaHSD2 was unaffected.
- Cortisol, but not progesterone, increased 11betaHSD1 mRNA and enhanced IL-1alpha's effect, while suppressing COX-2.
- PSE cells showed lower basal 11-oxoreductase activity than OSE cells; IL-1alpha did not significantly increase PSE cell activity.
Conclusions:
- Human PSE cells respond to IL-1alpha and steroids similarly to OSE cells.
- Lower basal and IL-1alpha-unresponsive 11betaHSD1 enzymatic activity in PSE cells may contribute to peritoneal adhesion formation.
- This contrasts with scar-free healing observed in OSE cells after ovulation.
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