SAR150640, a selective beta3-adrenoceptor agonist, prevents human myometrial remodelling and activation of matrix metalloproteinase in an in vitro model of chorioamnionitis.

British Journal of Pharmacology
Fréderic LirussiM Bardou

Abstract

The uterine pathophysiology underlying inflammatory conditions such as chorioamnionitis remains largely unclear. As we have shown that beta(3)-adrenoceptors act as regulators of myometrial inflammation, we wanted to investigate the potential role of beta(3)-adrenoceptors in preventing uterine remodelling induced by inflammation. The consequences of human chorioamnionitis on myometrial remodelling were characterized by Sirius Red staining and metalloproteinase (MMP) expression, and compared with the effects of incubating human myometrial samples with Escherichia coli lipopolysaccharide (LPS) in vitro. We also assessed the effect of SAR150640, a selective beta(3)-adrenoceptor agonist, on the production and activity of MMPs. Chorioamnionitis was associated with a 46% decrease in total collagen, as well as over-expression of MMP2 (+61%) and MMP9 (+84%); both effects were reproduced by incubation with LPS (10 microg x mL(-1), 48 h). LPS-induced over-expression of MMP2 and MMP9 in normal human myometrium was paralleled by an overactivity of the proteins. Both over-expression and overactivity were prevented by the beta(3)-adrenoceptor agonist SAR150640 in a concentration-dependent manner. SAR150640, by itself, did not exhibit any effe...Continue Reading

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Citations

Mar 1, 2012·British Journal of Pharmacology·A Rietz, Jp Spiers
Nov 14, 2016·The Journal of Physiological Sciences : JPS·Beata ModzelewskaAnna Kostrzewska
May 23, 2013·American Journal of Alzheimer's Disease and Other Dementias·Khanh vinh quoc Luong, Lan Thi Hoàng Nguyen
May 22, 2013·American Journal of Alzheimer's Disease and Other Dementias·Khanh vinh quoc Lương, Lan Thi Hoàng Nguyen
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Mar 1, 2021·Gynecologic and Obstetric Investigation·Beata ModzelewskaMaciej Jóźwik

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