Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Long regarded as proinflammatory molecules, prostaglandins (PGs) also have anti-inflammatory effects. Both prostaglandin D2 (PGD2) and its dehydration end product 15-deoxy-Delta-prostaglandin J2 (15d-PGJ2) seem to play important roles in regulating inflammation, via both receptor-dependent (DP1 and DP2 receptors) and receptor-independent mechanisms. Intracellular effects of PGD2 and 15d-PGJ2 that may suppress inflammation include inhibition of nuclear factor-kappaB (NF-kappaB) by multiple mechanisms (IkappaB kinase inhibition and blockade of NF-kappaB nuclear binding) and activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). ⋯ Indeed, classic inhibitors of PG synthesis such as nonselective and cyclooxygenase-2 (COX-2) selective inhibitors (nonsteroidal anti-inflammatory drugs) may actually prolong inflammation when administered during the resolution phase. These effects may regulate not only tissue inflammation but also vascular disease, possibly shedding light on the controversy surrounding nonsteroidal anti-inflammatory drug use and its relation to myocardial infarction. In this review, we summarize the current understanding of PGs as dichotomous molecules in the inflammatory process.