The role of cyclooxygenase-2 in oxidative stress and inflammation: Implications for poultry health and production

Oxidative stress and inflammation commonly occur in modern poultry farming, where they are closely linked mechanistically during the progression of disease and adaptation to stressors. This review synthesizes current evidence to outline cyclooxygenase-2 (COX-2) and downstream prostaglandin E2 (PGE₂) signaling via EP receptors as a key molecular nexus that connects excessive reactive oxygen species (ROS) with sustained inflammatory damage. In poultry, a range of stressors, such as heat stress, high stocking density, mycotoxin exposure, heavy metals, and pathogen challenges, promote ROS accumulation from sources such as mitochondria and NADPH oxidase (NOX). These disruptions in redox balance trigger regulatory pathways involving MAPK and NF-κB/AP-1, thereby upregulating PTGS2 (the gene for COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1), leading to increased PGE₂ production. In turn, the PGE₂/EP signaling pathway can enhance NOX activity, alter both innate and adaptive immune functions, and exacerbate barrier dysfunction in the intestine, liver, respiratory mucosa, and immune-related organs, establishing a reinforcing loop of ROS, COX-2, and PGE₂. We further discuss how the effects of COX-2 vary by tissue and pathogen, contributing to slowed growth, disrupted immunity, enhanced viral susceptibility, and damage to organs, and discuss potential intervention approaches such as Nrf2-focused antioxidants, nutrients that strengthen barriers, and targeted modulation of COX-2 and mPGES-1 activity and EP receptor signaling to disrupt the link between oxidative load and escalating inflammation. Finally, we outline a framework integrating standardized stress and pathogen challenges with eicosanoid and EP receptor profiling to guide targeted interventions on the COX-2 prostaglandin network in poultry.