Regulation of 11beta-hydroxysteroid dehydrogenase type 1 gene expression in human ovarian surface epithelial cells by interleukin-1.
BACKGROUND
Local modulation of 11beta-hydroxysteroid dehydrogenase (11betaHSD) activity, to promote increased availability of anti-inflammatory glucocorticoids, is proposed as a compensatory response to inflammatory stimuli. Human 11betaHSD type 1 (11betaHSD1) is principally an 11-oxoreductase that reversibly reduces cortisone to cortisol.


METHODS
Since ovulation is an acute inflammatory process, we examined the influence of pro-inflammatory cytokines on expression of 11betaHSD1 mRNA and metabolism of cortisone to cortisol by human ovarian surface epithelium (HOSE) in vitro.


RESULTS
Northern analysis showed an approximately 1.5 kb-sized 11betaHSD1 mRNA transcript in total RNA that was up-regulated approximately 3-fold by interleukin (IL)-1alpha (0.5 ng/ml) at 24 h. By real-time RT-PCR, induction of 11betaHSD1 mRNA by IL-1alpha was measurable at 6 h and maximal at 12 h. Primary HOSE cell cultures also showed low-level 11-oxoreductase activity that was stimulated time- and dose-dependently by IL-1alpha and IL-1beta. The 11betaHSD1 mRNA and 11-oxoreductase responses to 0.5 ng/ILalpha were both suppressed by IL-1 receptor antagonist (25 ng/ml).


CONCLUSIONS
Cultured HOSE cells express IL-1-responsive 11betaHSD1 and 11-oxoreductase activity mRNA in vitro. An 11betaHSD1-catalysed increase in anti-inflammatory glucocorticoid activity caused by pro-inflammatory cytokines could contribute to the local resolution of inflammation during ovulation.
Yong
Peter Y K
PY
Assisted Conception Programme, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
Harlow
Christopher
C
Thong
K J
KJ
Hillier
Stephen G
SG
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008875:Middle Aged; D010053:Ovary / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D042842:11-beta-Hydroxysteroid Dehydrogenases; C468386:HSD11B1 protein, human