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Keywords:

  • blood–brain barrier;
  • cerebral capillaries;
  • microglia;
  • NF-κB;
  • pro-inflammatory cytokines

Prostaglandin E2, a product of the cyclooxygenation of arachidonic acid released from membrane phospholipids, plays major roles in regulating brain injury and inflammation. Although prostaglandin E2 has frequently been considered as a possible inducer of brain damage and degeneration, it may exert beneficial effects in the CNS. Indeed, in spite of its classic role as a pro-inflammatory molecule, several recent in vitro observations indicate that prostaglandin E2 can inhibit microglial activation. This study investigated the effect of central prostaglandin E2 injection on circulating lipopolysaccharide-induced gene expression of different pro-inflammatory molecules in both vascular and parenchymal elements of the brain. Localized, but strong, expression of tumor necrosis factor-α and interleukin-1β mRNA was found at the edge of the intracerebroventricular tract, which was largely prevented by the central prostaglandin E2 injection. Systemic lipopolysaccharide injection caused a profound transcriptional activation of cyclooxygenase-2 and the inhibitory factor κBα (IκBα, index of NF-κB activity) in the cerebral endothelium and tumor necrosis factor-α in microglial cells across the brain parenchyma. Although exogenous prostaglandin E2 increased lipopolysaccharide-induced NF-κB activity and cyclooxygenase-2 transcription in vascular-associated elements, it significantly reduced microglial activation and tumor necrosis factor-α expression in the brain parenchyma. These results indicate that prostaglandin E2 may play an important role in modulating the immune response occurring at the injured site and the pro-inflammatory signaling events taking place in both vascular- and microglial-associated elements of the CNS.