AH has received research funding from AstraZeneca (3000 Euro consultancy and lecture fees 150.000 Euro research funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: RP is employed by Oxagen, which is in the process of developing CRTH2 antagonists for clinical use. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: Akos Heinemann has received research funding from AstraZeneca. Received: DecemAccepted: FebruPublished: March 19, 2012Ĭopyright: © 2012 Schröder et al. PLoS ONE 7(3):Įditor: Roland Seifert, Medical School of Hannover, United States of America (2012) PGH 1, the Precursor for the Anti-Inflammatory Prostaglandins of the 1-series, Is a Potent Activator of the Pro-Inflammatory Receptor CRTH2/DP2. Together, our results identify PGH 1 as an important lipid intermediate and novel CRTH2 agonist which may trigger CRTH2 activation in vivo in the absence of functional prostaglandin D synthase.Ĭitation: Schröder R, Xue L, Konya V, Martini L, Kampitsch N, Whistler JL, et al. All these effects are abrogated in the presence of the CRTH2 specific antagonist TM30089.
Physiological relevance of CRTH2 ligation by PGH 1 is demonstrated in several primary human hematopoietic lineages, which endogenously express CRTH2: PGH 1 mediates migration of and Ca 2+ flux in Th2 lymphocytes, shape change of eosinophils, and their adhesion to human pulmonary microvascular endothelial cells under physiological flow conditions. PGH 1 specifically internalizes CRTH2 in stable CRTH2 transfectants as assessed by antibody feeding assays. The PGH 1 precursor DGLA and the other PGH 1 metabolites did not display such effect. Non-invasive, real time dynamic mass redistribution analysis of living human CRTH2 transfectants and Ca 2+ flux studies reveal that PGH 1 activates CRTH2 as PGH 2, PGD 2 or PGD 1 do.
Herein we present evidence that PGH 1 is a potent activator of the pro-inflammatory PGD 2 receptor CRTH2, an attractive therapeutic target to treat allergic diseases such as asthma and atopic dermatitis. Prostaglandin H 1 (PGH 1) is the cyclo-oxygenase metabolite of dihomo-γ-linolenic acid (DGLA) and the precursor for the 1-series of prostaglandins which are often viewed as “anti-inflammatory”.
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