|
Academic/Biomedical Research
News & Jobs
|
|
|
|
|
|
|
|
|
|
|
|
|
Free Newsletters
Archive
My Subscriptions
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers
Regional News
US & Canada
Biotech Bay
Biotech Beach
Genetown
Pharm Country
BioCapital
BioMidwest
Bio NC
BioForest
Southern Pharm
BioCanada East
US Device
Europe
Asia
Company Profiles
Research Store
Research Events
Post an Event
Real Estate
Business Opportunities
|
|
|
|
PLoS By Category | Recent
PLoS Articles
|
|
Biochemistry - Diabetes and Endocrinology - Obstetrics - Physiology
|
Progesterone Acts via the Nuclear Glucocorticoid Receptor to Suppress IL-1ß-Induced COX-2 Expression in Human Term Myometrial Cells
Published:
Wednesday, November 28, 2012
Author:
Kaiyu Lei et al.
by Kaiyu Lei, Li Chen, Ektoras X. Georgiou, Suren R. Sooranna, Shirin Khanjani, Jan J. Brosens, Phillip R. Bennett, Mark R. Johnson
Progesterone is widely used to prolong gestation in women at risk of preterm labour (PTL), and acts at least in part via the inhibition of inflammatory cytokine-induced prostaglandin synthesis. This study investigates the mechanisms responsible for this inhibition in human myometrial cells. We used reporter constructs to demonstrate that interleukin 1beta (IL-1ß) inhibits progesterone driven PRE activation via p65 activation and that IL-1ß reduced progesterone driven gene expression (FKBP5). Conversely, we found that the activity of a p65-driven NF?B reporter construct was reduced by overexpression of progesterone receptor B (PRB) alone and that this was enhanced by the addition of MPA and that both MPA and progesterone suppressed IL-1ß-driven cyclo-oxygenase-2 (COX-2) expression. We found that over-expressed Halo-tagged PRB, but not PRA, bound to p65 and that in IL-1ß-treated cells, with no overexpression of either PR or p65, activated p65 bound to PR. However, we found that the ability of MPA to repress IL-1ß-driven COX-2 expression was not enhanced by overexpression of either PRB or PRA and that although the combined PR and GR antagonist Ru486 blocked the effects of progesterone and MPA, the specific PR antagonist, Org31710, did not, suggesting that progesterone and MPA act via GR and not PR. Knockdown using siRNA confirmed that both MPA and progesterone acted via GR and not PR or AR to repress IL-1ß-driven COX-2 expression. We conclude that progesterone acts via GR to repress IL-1ß-driven COX-2 activation and that although the interaction between p65 and PRB may be involved in the repression of progesterone driven gene expression it does not seem to be responsible for progesterone repression of IL-1ß-induced COX-2 expression.
More...
|
|
|
 |
|
|
|
|
|
|
|
|