title: Analysis of G-Protein Coupled Receptor 30 (GPR30) on Endothelial Inflammation.
abstract: 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.
authors.affiliation: Department of Obstetrics & Gynecology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Chakrabarti
authors.affiliation: Department of Obstetrics & Gynecology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada. sandra.davidge@ualberta.ca.|Department of Physiology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada. sandra.davidge@ualberta.ca.
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000517:prevention & control; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D057188:Workflow
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D004965:Estrogen Antagonists; D004967:Estrogens; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha
keywords: DPN; Endothelium; Estrogen; G-1; G-1 5; GPER; GPR30; HUVEC; Inflammation; PPT; TNF