Analysis of G-Protein Coupled Receptor 30 (GPR30) on Endothelial Inflammation
The female sex hormone estrogen (the most common form 17-β-estradiol or E2) is known to have both anti-inflammatory and pro-inflammatory effects. Given the diversity of estrogen responses mediated through its three distinct receptors, namely, estrogen receptor α (ERα), ERβ, and the G-protein coupled receptor 30 (GPR30), it is plausible that different receptors have specific modulatory effects on inflammation in different tissues. We have shown that activation of GPR30 exerted anti-inflammatory effects as demonstrated by significant attenuation of tumor necrosis factor (TNF)-mediated upregulation of adhesion molecules in isolated human umbilical vein endothelial cells. Interestingly, estrogen alone had no such effect and blockade of classical ERs restored the anti-inflammatory effect, suggesting that this effect was dependent on GPR30 and opposed to classical ERs. These findings were further validated by the negation of anti-inflammatory GPR30 effects by classical ER agonists. This chapter focuses on multiple pharmacological options to activate GPR30 and the use of TNF activated endothelial cells as a model system for inflammatory response as assessed by adhesion molecule detection through western blotting.
Key wordsEstrogen Endothelium Inflammation GPER GPR30 TNF HUVEC PPT DPN G-1 G-15
Dr. Davidge is a Canada Research Chair (CRC) in Maternal and Perinatal Cardiovascular Health. The Davidge laboratory receives funding from the Canadian Institutes of Health Research (CIHR), the Women and Children’s Health Research Institute (WCHRI) and the Heart and Stroke Foundation of Canada (HSF).