Microsomal Prostaglandin E Synthase-1 in Respiratory Diseases
Microsomal prostaglandin E synthase-1 [mPGES-1] is today a well recognized target for the development of nextgeneration anti-inflammatory drugs with improved selectivity and safety compared to nonsteroidal anti-inflammatory drugs [NSAIDs]. mPGES-1 is a terminal prostaglandin E2 [PGE2] synthase in the cyclooxygenase pathway. Among the three PGE synthases, namely cytosolic prostaglandin E synthase [cPGES], mPGES-1, and mPGES-2, mPGES-1 is the major isoform for producing PGE2 during inflammation. PGE2 is the major eicosanoid product of the respiratory system and is overproduced and secreted by the airway epithelium, smooth muscle, dendritic cells, macrophages, and fibroblasts in airway inflammatory diseases, including chronic obstructive pulmonary disease [COPD], acute lung inflammation, allergic asthma, and cancer. Recent studies using mPGES-1 knockout mice demonstrated that mPGES-1 contributes to the inflammatory PGE2 production involved in airway inflammation and respiratory regulation. In this review, we focus on mPGES-1 in respiratory diseases with the aim to cover the most recent advances in the understanding of mPGES-1 in airway inflammation, COPD, allergic airway diseases, respiratory response to hypoxia, and lung cancers.