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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3243-3250. Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-07-2772. This Article Full Text (PDF) All Versions of this Article: 2005-07-2772v1 107/8/3243    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Feng, C. Articles by Boyce, J. A Search for Related Content PubMed PubMed Citation Articles by Feng, C. Articles by Boyce, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2005 Accepted December 5, 2005 Human mast cells express multiple EP receptors for prostaglandin E2 that differentially modulate activation responses Chunli Feng, Elizabeth M Beller, Savita Bagga, and Joshua A Boyce* Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA; Partners Asthma Center, Boston, MA, USA * Corresponding author; email: jboyce{at}rics.bwh.harvard.edu. Prostaglandin (PG) E2 blocks mast cell (MC)-dependent allergic responses in humans but activates MCs in vitro. We assessed the functions of the EP receptors for PGE2 on cultured human MCs (hMCs). hMCs expressed the EP3, EP2 and EP4 receptors. PGE2 stimulated the accumulation of cyclic adenosine monophosphate (cAMP), and suppressed both FcRI -mediated eicosanoid production and necrosis factor- (TNF-) generation. PGE2 also caused phosphorylation of extracellular signal regulated kinase (ERK), exocytosis, and production of prostaglandin (PG)D2, as well as leukotriene (LT)C4 when protein kinase A (PKA) was inhibited. An EP3 receptor-selective agonist, AE-248, mimicked PGE2-mediated ERK phosphorylation, exocytosis, and eicosanoid formation. Selective agonists of both EP2 and EP4 receptors (AE1-259-01 and AE-329, respectively) stimulated cAMP accumulation. No selective agonist, alone or in combination, was as effective as PGE2. AE-248, AE1-259-01, and AE-329 all inhibited FcRI-mediated TNF- generation, while AE1-259-01 blocked eicosanoid production. PGE2 caused the expression of inducible cAMP early repressor (ICER) by a pathway involving PKA and ERK. Thus while PGE2 activates MCs through EP3 receptors, it also counteracts FcRI-mediated eicosanoid production through EP2 receptors and PKA, and blocks cytokine transcription. These functions explain the potency of PGE2 as a suppressor of early- and late-phase allergic responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Sakanaka, S. Tanaka, Y. Sugimoto, and A. Ichikawa Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1427 - C1433. [Abstract] [Full Text] [PDF] G. Natarajan, S. Ramalingam, I. Ramachandran, R. May, L. Queimado, C. W. Houchen, and S. Anant CUGBP2 downregulation by prostaglandin E2 protects colon cancer cells from radiation-induced mitotic catastrophe Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1235 - G1244. [Abstract] [Full Text] [PDF] C. L. Weller, S. J. Collington, A. Hartnell, D. M. Conroy, T. Kaise, J. E. Barker, M. S. Wilson, G. W. Taylor, P. J. Jose, and T. J. Williams Chemotactic action of prostaglandin E2 on mouse mast cells acting via the PGE2 receptor 3 PNAS, July 10, 2007; 104(28): 11712 - 11717. [Abstract] [Full Text] [PDF]

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