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Inflammation Research

, Volume 58, Supplement 2, pp S244–S248 | Cite as

Prostaglandin E Receptor Subtypes EP2 and EP4 Promote TH1 Cell Differentiation and TH17 Cell Expansion Through Different Signaling Modules

  • Daiji Sakata
  • Chengcan Yao
  • Yoshiyasu Esaki
  • Youxian Li
  • Toshiyuki Matsuoka
  • Kenji Kuroiwa
  • Yukihiko Sugimoto
  • Shuh Narumiya
Mini-papers for Young Investigator’s Award Contestants’ Session (Van Arman Award) Mini-Paper 4
  • 64 Downloads

Abstract

It is well known that prostaglandin (PG) E2 exerts T cell suppression in vitro through elevating cAMP by its receptors, EP2 and EP4. However, such an action is rarely detected in vivo, leaving PGE2-mediated immunosuppression an enigma. Here we show that under strong TCR stimulation, PGE2 facilitates T helper-1 (TH-1) differentiation through activation of phosphatidylinositol-3-kinase (PI3K) by EP2 and EP4. The PGE2-EP4 signaling is also required for IL-23 production by activated dendritic cells (DCs), and the PGE2-EP2/EP4 signaling amplifies IL-23-mediated TH-17 cell expansion. Administration of an EP4-selective antagonist in vivo to mice subjected to experimental allergic encephalomyelitis (EAE) decreases accumulation of both TH-1 and TH-17 cells in regional lymph nodes, and suppresses the disease progression. These results suggest PGE2 promotes immune inflammation through TH-1 differentiation and TH-17 expansion and the EP4 antagonism is therapeutically useful for various immune diseases.

Keywords

PGE2 Wortmannin Experimental Allergic Encephalomyelitis Myelin Oligodendrocyte Glycoprotein Immune Inflammation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag, Basel 2009

Authors and Affiliations

  • Daiji Sakata
    • 1
  • Chengcan Yao
    • 1
  • Yoshiyasu Esaki
    • 1
  • Youxian Li
    • 1
  • Toshiyuki Matsuoka
    • 1
  • Kenji Kuroiwa
    • 2
  • Yukihiko Sugimoto
    • 2
  • Shuh Narumiya
    • 1
  1. 1.Department of Pharmacology, Faculty of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Physiological Chemistry, Faculty of Pharmaceutical SciencesKyoto UniversityKyotoJapan

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