SAR150640, a selective beta3-adrenoceptor agonist, prevents human myometrial remodelling and activation of matrix metalloproteinase in an in vitro model of chorioamnionitis
| Autor: | F, Lirussi, M, O'Brien, M, Wendremaire, F, Goirand, P, Sagot, M, Dumas, J J, Morrison, M, Bardou |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Sulfonamides Dose-Response Relationship Drug Blotting Western Adrenergic beta-3 Receptor Agonists In Vitro Techniques Benzoates Models Biological Propranolol Research Papers Matrix Metalloproteinases Chorioamnionitis Pregnancy Myometrium Humans Female Adrenergic beta-3 Receptor Antagonists |
| Zdroj: | British journal of pharmacology. 159(6) |
| ISSN: | 1476-5381 |
| Popis: | 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 effect on MMP production in control tissues.This study shows that inflammation was associated with an intense remodelling of human myometrium, a process likely to be explained by MMP activation. Our study emphasizes the potential therapeutic relevance of beta(3)-adrenoceptor agonists to the treatment of preterm labour and other uterine inflammatory conditions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|