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.

TSG-6 Protein Is Crucial for the Development of Pulmonary Hyaluronan Deposition, Eosinophilia, and Airway Hyperresponsiveness in a Murine Model of Asthma

“…Interestingly, PGD 2 and its high affinity receptors DP1 and CRTH2 (chemoattractant-homologous receptor expressed on Th2 cells) have been shown to be crucial for the promotion and maintenance of allergic responses (51)(52)(53)(54)(55). Importantly, although PGD 2 promotes inflammatory responses through its CRTH2 receptor, which is selectively expressed on eosinophils, Th2 T cells, and basophils (54,55), PGD 2 also has anti-inflammatory and inhibitory effects on neutrophils (56,57).…”

Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology

“…Following crystallization in 1997, Kanaoka et al (49) proposed that h-PGDS contains a pocket that activates glutathione via Tyr-8, such that the glutathione thiol functions analogous to Cys-65 of l-PGDS. PGD 2 has two known receptors, DP 1 and chemoattractant receptor-homologous, molecule expressed on Th2 cells (CRTH2) (50). DP 1 belongs to the family of GPCR that includes IP, TP, EP [1][2][3][4] , and FP, and ligand binding leads to intracellular increases of cAMP.…”

Repeated application of glucocorticoids exacerbate pruritus via inhibition of prostaglandin D₂ production of mast cells in a murine model of allergic contact dermatitis

“…In contrast, H-PGDS is expressed and localized in immune and inflammatory cells such as mast cells (Urade et al, 1990), antigen-presenting cells (Urade et al, 1989) and Th2 cells (Tanaka et al, 2000). The effects of PGD 2 are mediated by a high-affinity interaction with D prostanoid receptor (DP) 1 and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) (Pettipher, 2008). Both these DPs belong to the G protein-coupled receptor family.…”