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The Anti-Inflammatory Effects of Prostaglandins

2009; SAGE Publishing; Volume: 57; Issue: 6 Linguagem: Inglês

10.2310/jim.0b013e31819aaa76

1708-8267

Jose U. Scher, Michael H. Pillinger,

NF-κB Signaling Pathways

Long regarded as proinflammatory molecules, prostaglandins (PGs) also have anti-inflammatory effects. Both prostaglandin D 2 (PGD 2 ) and its dehydration end product 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) seem to play important roles in regulating inflammation, via both receptor-dependent (DP 1 and DP 2 receptors) and receptor-independent mechanisms. Intracellular effects of PGD 2 and 15d-PGJ 2 that may suppress inflammation include inhibition of nuclear factor-κB (NF-κB) by multiple mechanisms (IκB kinase inhibition and blockade of NF-κB nuclear binding) and activation of peroxisome proliferator-activated receptor-γ (PPAR-γ). Prostaglandin F 2α (PGF 2α ) may also have important anti-inflammatory effects, although current data are limited. In animal models, expression of both PGD and PGF synthases declines during acute inflammation, only to rise again during the resolution phase, suggesting their possible role in resolving inflammation. Prostaglandin E 2 (PGE 2 ), the classic model of a proinflammatory lipid mediator, also has anti-inflammatory effects that are both potent and context dependent. Thus, accumulating data suggest that PGs not only participate in initiation, but may also actively contribute to the resolution of inflammation. 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.