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Drug News Perspect 2008, 21(6): 317
ISSN 0214-0934
Copyright 2008 Clarivate
CCC: 0214-0934
 


Vol. 21, No. 6, July/August 2008


LOOKING AHEAD

The central role played by CRTH2 in mediating various effects suggests that antagonism of this receptor is an attractive approach to the treatment of chronic allergic disease.

Antagonists of the Prostaglandin D2 Receptor CRTH2*

by Roy Pettipher and Trevor T. Hansel



Summary

Prostaglandin D2 (PGD2) is produced by mast cells, Th2 lymphocytes and dendritic cells and causes activation of Th2 lymphocytes, eosinophils and basophils through a high-affinity interaction with the G protein-coupled receptor chemoattractant homologous receptor expressed on Th2 cells (CRTH2, also known as DP2). Activation of CRTH2 induces chemotaxis of Th2 lymphocytes and eosinophils and has the unusual property of promoting cytokine production by Th2 lymphocytes in the absence of allergen or co-stimulation. The ability of supernatants from immunologically activated mast cells to activate Th2 cells and eosinophils is mediated by CRTH2. This receptor also plays an important role in amplifying allergic responses through paracrine activation of Th2 cells. Pharmacological blockade or genetic ablation of CRTH2 is associated with a reduction in airways inflammation and reduced levels of mucus, Th2 cytokines and immunoglobulin E. The central role played by CRTH2 in mediating these effects suggests that antagonism of this receptor is an attractive approach to the treatment of chronic allergic disease. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.



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