title: CRTH2 and D-type prostanoid receptor antagonists as novel therapeutic agents for inflammatory diseases.
abstract: Accumulation of type 2 T helper (Th2) lymphocytes and eosinophils is a hallmark of bronchial asthma and other allergic diseases, and it is believed that these cells play a crucial pathogenic role in allergic inflammation. Thus, Th2 cells and eosinophils are currently considered a major therapeutic target in allergic diseases and asthma. However, drugs that selectively target the accumulation and activation of Th2 cells and eosinophils in tissues are unavailable so far. Prostaglandin (PG)D(2) is a key mediator in various inflammatory diseases including allergy and asthma. It is generated by activated mast cells after allergen exposure and subsequently orchestrates the recruitment of inflammatory cells to the tissue. PGD(2) induces the chemotaxis of Th2 cells, basophils and eosinophils, stimulates cytokine release from these cells and prolongs their survival, and might hence indirectly promote IgE production. PGD(2) mediates its biologic functions via 2 distinct G protein-coupled receptors, D-type prostanoid receptor (DP), and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). DP and CRTH2 receptors are currently being considered as highly promising therapeutic targets for combating allergic diseases and asthma. Here, we revisit the roles of PGD(2) receptors in the regulation of eosinophil and Th2 cell function and the efforts towards developing candidate compounds for clinical evaluation.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Rufina
authors.initials: R
authors.lastname: Schuligoi
authors.forename: Eva
authors.initials: E
authors.lastname: Sturm
authors.forename: Petra
authors.initials: P
authors.lastname: Luschnig
authors.forename: Viktoria
authors.initials: V
authors.lastname: Konya
authors.forename: Sonia
authors.initials: S
authors.lastname: Philipose
authors.forename: Miriam
authors.initials: M
authors.lastname: Sedej
authors.forename: Maria
authors.initials: M
authors.lastname: Waldhoer
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Peskar
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015230:Prostaglandin D2 / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor