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SHR Neuro Cancer Cardio Metab Microb Lipid

Prostaglandin D2 als Mediator der Allergie

Abstract: Prostaglandin (PG) D2 is released by mast cells during the allergic response. Others and our group have recently produced considerable evidence that PGD2 might be involved in the initiation and perpetuation of allergic inflammation by orchestrating the recruitment of eosinophil granulocytes to the tissue, where they might cause tissue damage and induce the symptoms of allergic inflammation. The biological effects of PGD2 are mediated by three distinct receptors, the DP receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), or at higher concentrations by the thromboxane receptor, TP. Small molecule antagonists of these receptors have recently become available and are currently being developed for the treatment of inflammatory diseases, such as bronchial asthma and eczema. However, the relative contributions of DP, CRTH2 and TP to PGD2-induced biological responses have still remained unclear, but the knowledge thereof is mandatory in order to predict which of these receptors are the most promising targets for the treatment of allergic disease and highlight their potential limitations. Eosinophil function will be investigated with respect to the release of eosinophils from the bone marrow, their recruitment into the tissue, the cells life span, and the release of pro-inflammatory mediators from eosinophils, such as reactive oxygen species, leukotrienes or exocytosed toxic granule contents. Moreover, we will test the potential clinical usefulness of CRTH2 and DP antagonists in vivo, using a murine model of ovalbumin-induced allergic pulmonary inflammation and airway hyperresponsiveness. Since the different biological responses to PGD2 can be mediated by CRTH2 or DP, respectively, a combined therapy with CRTH2 plus DP antagonists also needs to be given consideration. The study might hence lead to novel therapeutic regimens for the treatment of allergic inflammation and asthma.

Project Leader:: Heinemann Akos

Duration:: 01.05.2007-31.03.2011

Programme:: Einzelprojekt

Type of Research: basic research

Staff: Heinemann, Akos, Project Leader; Lippe, Irmgard Theresia, Co-worker; Peskar, Bernhard, Co-worker

MUG Research Units: Division of Pharmacology

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > D-type prostanoid receptor enhances the signaling ... J Allergy Clin Immunol. 2012; 129(2): 500.e1- 500.e9; > Interaction of eosinophils with endothelial cells ... Eur J Immunol. 2011; 41(8):2379-2389; > Inhibitory effect of prostaglandin I2 on bone marr... J Leukoc Biol. 2011; 90(2):285-291; > Endothelium-derived prostaglandin I(2) controls th... J Allergy Clin Immunol. 2010; 125(5): 1105-1113.; > The Prostaglandin E2 Receptor EP4 Is Expressed by ... Arterioscler Thromb Vasc Biol. 2010; 30(12): 2416-2423.; > Prostaglandin H2 induces the migration of human eo... J Leukoc Biol. 2009; 85(1): 136-145.; > Differential involvement of Ca2+ and actin filamen... Pharmacology. 2009; 83(3): 131-140.; > The role of eicosanoids on the chemotactic respons... [ Dissertation ] Graz Medical University; 2008. pp.145.; > Effects of PGD2 and its metabolites on eosinophil ... [ Diplomarbeit/Master Thesis ] Graz Medical University; 2008. pp.80.; > The role of prostaglandin D2 receptors in the biol... [ Dissertation ] Graz Medical University ; 2008. pp.120.