The opposing role of two prostaglandin D2 receptors, DP and CRTH2, in human eosinophil migration

Takahito Chiba, Shigeharu Ueki, Wataru Ito, Hikari Kato, Rie Kamada, Masahide Takeda, Hiroyuki Kayaba, Masutaka Furue, Junichi Chihara

研究成果: ジャーナルへの寄稿記事

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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. Conclusion: Taken together, the balance between DP and CRTH2 could influence the degree of PGD2-induced eosinophil migration and DP agonist might regulate eosinophil activation.

元の言語英語
ページ(範囲)511-517
ページ数7
ジャーナルAnnals of Allergy, Asthma and Immunology
106
発行部数6
DOI
出版物ステータス出版済み - 6 1 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

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