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Anti-inflammation therapy by activation of prostaglandin EP4 receptor in cardiovascular and other inflammatory diseases.

Abstract
Prostaglandin E2 constitutes a major cyclooxygenase-2-derived prostanoid produced at inflammatory sites. In vitro and in vivo data support its role as a modulator of inflammation. Prostaglandin E2 exerts anti-inflammatory effects by binding to one of its receptors, the prostaglandin E receptor 4 (EP4), thereby modulating macrophage and T lymphocyte functions that participate crucially in innate and adaptive immunity and tissue remodeling and repair. The activation of EP4 suppresses the release of cytokines and chemokines from macrophages and T cells, inhibits the proliferation and the activation of T cells, and induces T-cell apoptosis. Lack of EP4 in bone marrow-derived cells accelerates local inflammation in atherosclerotic and aneurysm lesions and increases the prevalence of aneurysm formation. An EP4 agonist promotes graft survival in allograft cardiac transplantation and dampens tissue damage after myocardial ischemia. Anti-inflammatory actions of EP4 agonism may benefit other inflammatory disorders, including colitis and gastric ulcers. By contrast, EP4 acts as a proinflammatory mediator in encephalomyelitis, skin inflammation, and arthritis by promoting T helper (Th) 1 differentiation and Th17 expansion. Overall, EP4 activation produces powerful anti-inflammatory responses in many experimental diseases, rendering EP4 agonists attractive agents to attenuate syndromes associated with inflammation.
AuthorsEva H C Tang, Peter Libby, Paul M Vanhoutte, Aimin Xu
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 59 Issue 2 Pg. 116-23 (Feb 2012) ISSN: 1533-4023 [Electronic] United States
PMID21697732 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Receptors, Prostaglandin E, EP4 Subtype
  • Cyclooxygenase 2
  • Dinoprostone
Topics
  • Animals
  • Anti-Inflammatory Agents (pharmacology, therapeutic use)
  • Apoptosis
  • Cardiovascular Diseases (drug therapy, physiopathology)
  • Cyclooxygenase 2 (metabolism)
  • Dinoprostone (metabolism)
  • Humans
  • Inflammation (drug therapy, physiopathology)
  • Inflammation Mediators (metabolism)
  • Macrophages (metabolism)
  • Receptors, Prostaglandin E, EP4 Subtype (agonists, metabolism)
  • T-Lymphocytes (metabolism)

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