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Anti‐inflammatory effects of prostaglandin E 2 in the central nervous system in response to brain injury and circulating lipopolysaccharide
Author(s) -
Zhang Ji,
Rivest Serge
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00080.x
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , prostaglandin e2 , cyclooxygenase , prostaglandin , inflammation , microglia , prostaglandin e , prostaglandin d2 , biology , endocrinology , central nervous system , parenchyma , proinflammatory cytokine , immunology , medicine , pathology , biochemistry , enzyme
Prostaglandin E 2 , a product of the cyclooxygenation of arachidonic acid released from membrane phospholipids, plays major roles in regulating brain injury and inflammation. Although prostaglandin E 2 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 E 2 can inhibit microglial activation. This study investigated the effect of central prostaglandin E 2 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 E 2 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 E 2 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 E 2 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.