E prostanoid 2 (EP2)/EP4-mediated suppression of antigen-specific human T-cell responses by prostaglandin E2

Mitsuhiro Okano, Yuji Sugata, Tazuko Fujiwara, Rie Matsumoto, Masahiro Nishibori, Kenji Shimizu, Megumi Maeda, Yoshinobu Kimura, Shin Kariya, Hisashi Hattori, Minehiko Yokoyama, Kosuke Kino, Kazunori Nishizaki

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Prostaglandin E2 (PGE2) is a lipid mediator that displays important immunomodulatory properties, such as polarization of cytokine production by T cells. Recent investigations have revealed that the effect of PGE2 on cytokine production is greatly influenced by external stimuli; however, it is unclear whether PGE2 plays a significant role in major histocompatibility complex-mediated antigen-specific T-cell responses via binding to one of four subtypes of E prostanoid (EP) receptor alone or in combination. In the present study, we sought to determine the effect of PGE 2 on antigen-specific CD4+ T-cell responses in humans, especially in terms of receptor specificity. We used purified protein derivative (PPD) and Cry j 1 as T helper type 1 (Th1) and Th2-inducing antigens, respectively. We generated several different Cry j 1- and PPD-specific T-cell lines (TCLs). PGE2 significantly and dose-dependently inhibited the proliferation and subsequent production of interleukin-4 by Cry j 1-specific TCLs and of interferon-γ by PPD-specific TCLs upon antigen stimulation. Administration of EP2 receptor agonist and EP4 receptor agonist suppressed these responses in an adenylate cyclase-dependent manner, while EP1 and EP3 receptor agonists did not. Messenger RNA for EP2, EP3 and EP4, but not EP1, receptors were detected in Cry j 1- and PPD-specific TCLs, and no differences in EP receptor expression were observed between them. Furthermore, PGE2 and EP2 receptor agonist significantly inhibited interleukin-5 and interferon-γ production by peripheral blood mononuclear cells in response to Cry j 1 and PPD stimulation, respectively. These results suggest that PGE2 suppresses both Th1- and Th2-polarized antigen-specific human T-cell responses via a cAMP-dependent EP2/EP4-mediated pathway.

Original languageEnglish
Pages (from-to)343-352
Number of pages10
JournalImmunology
Volume118
Issue number3
DOIs
Publication statusPublished - Jul 1 2006

Keywords

  • Antigen
  • E prostanoid
  • Human
  • Prostaglandin E
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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