Inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 (COX-2) expression (iNOS/COX-2)

iNOS/COX-2 expression refers to the simultaneous induction of Inducible Nitric Oxide Synthase (iNOS) and Cyclooxygenase-2 (COX-2), two key enzymes that drive the inflammatory response (Surh et al., 2001, Nature Reviews Cancer). iNOS (NOS2) catalyzes the production of nitric oxide (NO), while COX-2 (PTGS2) is responsible for the synthesis of pro-inflammatory prostaglandins like PGE2 (UniProt P35228; UniProt P35354). These enzymes are typically co-expressed in response to inflammatory stimuli such as cytokines (e.g., TNF-alpha, IL-1beta) or bacterial lipopolysaccharides (LPS), primarily through the activation of the NF-kappaB transcription factor (StatPearls, 2023). In many therapeutic contexts, particularly in the study of natural products and anti-inflammatory agents, the ability to downregulate the expression of both enzymes is used as a primary indicator of anti-inflammatory efficacy (PubMed, PMID: 11483857). Overexpression of iNOS and COX-2 is linked to chronic inflammatory diseases, various cancers, and neurodegenerative conditions, making their dual modulation a significant area of pharmacological interest (NIH, 2023). Drugs targeting this expression typically act by inhibiting the upstream signaling pathways that lead to gene transcription or by directly inhibiting the catalytic activity of the resulting enzymes (PubChem, 2024).

Other names

iNOS/COX-2 pathwayNOS2/PTGS2 expressionInducible nitric oxide synthase and prostaglandin-endoperoxide synthase 2 expressionInflammatory mediator expression

Drugs targeting this pathway act either by suppressing the transcriptional induction of the NOS2 and PTGS2 genes (e.g., via inhibition of NF-κB or MAP kinase signaling) or by directly binding to and inhibiting the catalytic activity of the iNOS and COX-2 enzymes themselves (StatPearls, 2023; PubChem, 2024).