Prostaglandin E2 signaling pathway (PGE2 signaling)

Prostaglandin E2 (PGE2) signaling is a central inflammatory pathway initiated by the release of arachidonic acid from cell membranes, which is then converted into PGE2 by the sequential action of cyclooxygenase (COX-1 and COX-2) enzymes and prostaglandin E synthase (PGES) (Source: Nature Reviews Drug Discovery, PMID: 17443172). PGE2 acts as a potent lipid mediator that exerts its effects through four distinct G protein-coupled receptors, EP1 through EP4, which are widely distributed across various tissues and mediate diverse physiological responses including vasodilation, pain sensitization, and fever (Source: StatPearls, NBK549778). In pathological states, overactivation of this signaling axis contributes to chronic inflammation, autoimmune diseases, and the progression of various cancers by promoting tumor cell proliferation, angiogenesis, and immune evasion (Source: Pharmacology & Therapeutics, PMID: 23954645). Pharmacological modulation of this pathway is a cornerstone of anti-inflammatory therapy, primarily through the use of non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit COX enzymes, as well as emerging specific EP receptor antagonists and mPGES-1 inhibitors designed to minimize the side effects associated with broad prostaglandin suppression (Source: Journal of Lipid Research, PMID: 25339687). Additionally, PGE2 signaling plays a role in mucosal protection and bone metabolism, making its systemic inhibition a challenge due to potential off-target effects on the gastrointestinal and renal systems (Source: Frontiers in Pharmacology, PMID: 30804781). The pathway also interacts with other inflammatory mediators like cytokines and leukotrienes, creating a complex network that regulates the overall immune microenvironment (Source: Cell, PMID: 25193314).

Other names

Prostaglandin E2-related inflammatory signalingPGE2 pathwayCOX-2/mPGES-1/EP axisProstanoid E2 signaling

Inhibition of cyclooxygenase enzymes (COX-1 and COX-2) to reduce PGE2 synthesis; antagonism of specific prostaglandin E receptors (EP1-EP4); or agonism of EP receptors for mucosal protection or labor induction.