title: The opposing role of two prostaglandin D2 receptors, DP and CRTH2, in human eosinophil migration.
abstract: BACKGROUND
  Prostaglandin D2 (PGD2) regulates various immunological responses via two distinct PGD2 receptors, prostaglandin D receptor (DP), and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Recent studies have demonstrated that PGD2 induces the migration of eosinophils through CRTH2. Although human eosinophils express both DP and CRTH2, it is unclear whether the function of DP is involved in eosinophil migration.
  
  
  OBJECTIVE
  In this study, we investigated the roles of DP and CRTH2 in eosinophil migration by using selective agonists and antagonists.
  
  
  METHODS
  Eosinophils were isolated from human subjects with mild eosinophilia by modified CD16-negative selection. After stimulation with or without DP receptor agonist, eosinophil migration was measured by Boyden chamber. The effect of DP agonists on CRTH2-induced eosinophil migration was studied in terms of CRTH2 expression, Ca2+ mobilization, ERK/MAPK phosphorylation, and cyclic AMP (cAMP) production.
  
  
  RESULTS
  Treatment with DP agonists inhibited CRTH2-induced chemotaxis of eosinophils. Furthermore, we showed that DP agonists enhanced cAMP production in CRTH2 agonist stimulation without increasing CRTH2 expression. DP mediates eosinophils through the elevation of intracellular cAMP production but does not change CRTH2 expression.
  
  
  CONCLUSIONS
  Taken together, the balance between DP and CRTH2 could influence the degree of PGD2-induced eosinophil migration and DP agonist might regulate eosinophil activation.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. allheart@dermatol.med.kyushu-u.ac.jp
authors.forename: Takahito
authors.initials: T
authors.lastname: Chiba
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.forename: Hikari
authors.initials: H
authors.lastname: Kato
authors.forename: Rie
authors.initials: R
authors.lastname: Kamada
authors.forename: Masahide
authors.initials: M
authors.lastname: Takeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kayaba
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Junichi
authors.initials: J
authors.lastname: Chihara
mesh_terms: D015153:Blotting, Western; D002118:Calcium; D002478:Cells, Cultured; D002633:Chemotaxis; D000242:Cyclic AMP / Q000378:metabolism; D004802:Eosinophilia; D004804:Eosinophils / Q000276:immunology* / Q000502:physiology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015230:Prostaglandin D2 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; D015230:Prostaglandin D2; D002118:Calcium; C036293:prostaglandin D2 receptor