Prostaglandin E2 receptor 2 and 4 (EP2/EP4)

Prostaglandin E2 receptor 2 (EP2) and 4 (EP4) are G protein-coupled receptors that mediate the biological effects of Prostaglandin E2 (PGE2), a lipid mediator crucial for immune regulation (UniProt P43116, P35408). In the context of Mesenchymal Stem Cell (MSC) therapy, these receptors on immune cells are activated by MSC-secreted PGE2 to exert potent immunosuppressive effects (Aggarwal & Pittenger, 2005). Activation of EP2 and EP4 triggers the Gs-adenylate cyclase-cAMP signaling pathway, which inhibits the proliferation and activation of T cells, B cells, and Natural Killer cells (Najar et al., 2016). This signaling axis also promotes the differentiation of regulatory T cells (Tregs) and shifts macrophages from a pro-inflammatory M1 state to an anti-inflammatory M2 phenotype (PubMed 27114131). These receptors are significant therapeutic targets in inflammatory diseases, autoimmune conditions, and graft-versus-host disease due to their role in maintaining immune homeostasis. Conversely, in oncology, EP2 and EP4 are often targeted with antagonists to overcome the immunosuppressive tumor microenvironment that limits anti-tumor immunity (StatPearls, 2023). Drugs interacting with these receptors include agonists like dinoprostone for labor induction and antagonists like grapiprant for pain management (PubChem). The dual role of EP2/EP4 in both promoting tissue repair and potentially facilitating tumor growth necessitates precise therapeutic strategies.

Other names

PTGER2PTGER4Prostanoid EP2 receptorProstanoid EP4 receptorPGE2 receptor 2PGE2 receptor 4EP2EP4

Activation of EP2 and EP4 receptors by PGE2 triggers the Gs-protein-mediated adenylate cyclase pathway, increasing intracellular cAMP levels and activating protein kinase A (PKA), which leads to the suppression of pro-inflammatory cytokine production and the induction of immune tolerance.