PTGS2

PTGS2, or prostaglandin-endoperoxide synthase 2, encodes cyclooxygenase-2 (COX-2), an enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H2, the precursor of various prostanoids. COX-2 is the inducible isoform of the cyclooxygenase family, in contrast to COX-1, which is constitutively expressed in many tissues. COX-2 activity drives the production of prostaglandins involved in inflammation, fever, and pain, and it also participates in processes such as angiogenesis and tissue repair. In humans, COX-2 is expressed at low levels under resting conditions but is upregulated in response to inflammatory stimuli and cellular stress.

Regulation and expression of PTGS2 are complex. Its transcription is rapidly induced by inflammatory mediators such as interleukin-1, tumor necrosis factor-α, and lipopolysaccharide, as well as by growth factors. Transcription factors including NF-κB and AP-1 play important roles in PTGS2 upregulation. Post-transcriptional mechanisms also influence COX-2 levels, contributing to its transient expression during inflammation.

Physiological and pathological roles of COX-2 extend beyond inflammation. Prostaglandins produced via COX-2 participate in fever and pain signaling, as well as in renal and cerebral physiology. Overexpression of COX-2 has been observed in various cancers and is associated with tumor growth, angiogenesis, and resistance to apoptosis, making PTGS2 a focus of research in oncology and inflammatory diseases.

Clinically, COX-2 inhibitors (for example, celecoxib) were developed to reduce gastrointestinal toxicity associated with non-selective NSAIDs while providing anti-inflammatory effects. However, COX-2 inhibitors have been linked to cardiovascular risks and other adverse effects, leading to restricted use in certain populations. PTGS2 polymorphisms and expression levels can influence disease susceptibility and treatment responses, and the gene remains a key target in research on inflammation and cancer.