The therapeutic potential of CRTH2/DP2 beyond allergy and asthma

Abstract

Prostaglandin (PG) D has been in the focus of research for quite a long time, but its biological effects and its roles in human disease are still not fully characterized. When in 2001 a second major PGD receptor termed chemoattractant receptor homologue expressed on Th2 cells (CRTH2; alternative name DP2) was discovered, diverse investigations started to shed more light on the complex and often controversial actions of the prostaglandin. With various immunomodulating effects, such as induction of migration, activation, and cytokine release of leukocytes observed both in vivo and in vitro, CRTH2 has emerged as a promising target for the treatment of allergic diseases. However, with more and more research being performed on CRTH2, it has also become clear that its biological actions are far more diverse than expected at the beginning. In this review, we aim to summarize the roles that PGD - and CRTH2 in particular - might play in diseases of the central nervous system, kidney, intestine, lung, hair and skin, bone and cartilage, and in cancer. Based on current data we propose that blocking CRTH2 might be a potential therapeutic approach to numerous conditions beyond classical allergic diseases and asthma.

Lipid‐Embedded Molecular Dynamics Simulation Model for Exploring the Reverse Prostaglandin D2 Agonism of CT‐133 towards CRTH2 in the Treatment of Type‐2 Inflammation Dependent Diseases

“…Chemoattractant receptor homolog expressed on Th2 cells (CRTH2), alternatively known as D prostanoid receptor 2 (DP2), since its discovery in 2001, has spurred lots of research into its role in inflammation and other diseases . Though reliably established as a surface trait of Th2 cells, it is also expressed on eosinophils, basophils, and monocytes in humans .…”

“…Recent studies has also established the activities of CRTH2 beyond allergy and asthma to involve pro‐fibrotic and antifibrotic effects in the respiratory tract, abetting renal fibrosis and inflammation through repression of interleukin 4 and 13 as well as inflammation induced cancer . These activities of CRTH2 is in response to its activation by prostaglandin d2 (PGD2) and its metabolites …”

“…The inhibition of CRTH2 activation by PGD2 is of therapeutic importance in the control of the recruitment of pro‐inflammatory cells that express it . Several reports have confirmed the role of CRTH2 in many inflammation dependent diseases in almost all parts of the body . Severing the PGD2 influence on CRTH2 will therefore be a cutting‐edge approach in the treatment and control of most inflammatory diseases that depend on PGD2‐CRTH2 signaling.…”

“…[23,24] These activities of CRTH2 is in response to its activation by prostaglandin d2 (PGD2) and its metabolites. [3] The CRTH2 agonist, PGD2 is an eicosanoid that is principally released by mast cells [25,26] including antigen presenting cells, Th2 lymphocytes, [27] dendritic cells, [28] and eosinophils. [29] The biological impact of PGD2 and its metabolites 13,14-dihydro-15-keto-PGD2 (DK-PGD2) and PGJ2 is mediated by CRTH2 and other two G-protein-coupled receptors: D prostanoid receptor (DP1) and T prostanoid receptor (TP).…”

“…[17] Several reports have confirmed the role of CRTH2 in many inflammation dependent diseases in almost all parts of the body. [3] Severing the PGD2 influence on CRTH2 will therefore be a cutting-edge approach in the treatment and control of most inflammatory diseases that depend on PGD2-CRTH2 signaling. PGD2 possess a carboxylate group which has been conserved in most of the antagonists discovered.…”