The roles of the prostaglandin D2 receptors DP1 and CRTH2 in promoting allergic responses

Abstract

Prostaglandin D(2) (PGD(2)) is produced by mast cells, Th2 lymphocytes and dendritic cells and has been detected in high concentrations at sites of allergic inflammation. PGD(2) exerts its inflammatory effects through high affinity interactions with the G protein coupled receptors DP(1) and chemoattractant-homologous receptor expressed on Th2 cells (CRTH2, also known as DP(2)). DP(1) and CRTH2 act in concert to promote a number of biological effects associated with the development and maintenance of the allergic response. During the process of allergen sensitization, DP(1) activation may enhance polarization of Th0 cells to Th2 cells by inhibiting production of interleukin 12 by dendritic cells. Upon exposure to allergen in sensitized individuals, activation of DP(1) may contribute to the long lasting blood flow changes in the target organ. CRTH2 is expressed by Th2 lymphocytes, eosinophils and basophils and may mediate the recruitment of these cell types during the late phase allergic response. The role played by CRTH2 in promoting the production of Th2 cytokines and IgE make antagonism of this receptor a particularly attractive approach to the treatment of chronic allergic disease.