title: Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors.
abstract: Prostaglandin E2 (PGE2) is one of the most typical lipid mediators produced from arachidonic acid (AA) by cyclooxygenase (COX) as the rate-limiting enzyme, and acts on four kinds of receptor subtypes (EP1-EP4) to elicit its diverse actions including pyrexia, pain sensation, and inflammation. Recently, the molecular mechanisms underlying the PGE2 actions mediated by each EP subtype have been elucidated by studies using mice deficient in each EP subtype as well as several compounds highly selective to each EP subtype, and their findings now enable us to discuss how PGE2 initiates and exacerbates inflammation at the molecular level. Here, we review the recent advances in PGE2 receptor research by focusing on the activation of mast cells via the EP3 receptor and the control of helper T cells via the EP2/4 receptor, which are the molecular mechanisms involved in PGE2-induced inflammation that had been unknown for many years. We also discuss the roles of PGE2 in acute inflammation and inflammatory disorders, and the usefulness of anti-inflammatory therapies that target EP receptors. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Kohichi
authors.initials: K
authors.lastname: Kawahara
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hohjoh
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Inazumi
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Soken
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Electronic address: ysugi@kumamoto-u.ac.jp.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015232:Dinoprostone / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone
keywords: Helper T cell; Irritant contact dermatitis; Mast cell; Multiple sclerosis; Prostanoid