TNFalpha-induced cyclooxygenase 2 not only increases the vasopermeability of blood-brain barrier but also enhances the neutrophil survival in Escherichia coli-induced brain inflammation.
In Escherichia coli-induced brain inflammation, cyclooxygenase-2 was induced not only on brain arterioles at 3 h, but also on infiltrating neutrophils at 9 h post-intracerebral injection. Intravenous injection of E. coli or recombinant TNFalpha also induced cyclooxygenase-2 expression on arterioles. Cyclooxygenase-2 and TNFalpha were co-localized on the arterioles as well as the infiltrating neutrophils by serial-section staining, indicating that cyclooxygenase-2 was induced by TNFalpha. NS398 (a cyclooxygenase-2 selective inhibitor) not only inhibited the increase of blood-brain barrier permeability, but also enhanced the apoptosis of the infiltrating neutrophils after E. coli stimulation. This suggests that TNFalpha-stimulated cyclooxygenase-2 induction play an important role on E. coli-induced brain inflammation. Its inhibition would help the resolution of neutrophil-mediated brain inflammation.
Tsao
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N
Department of Microbiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Hsu
H P
HP
Lei
H Y
HY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier; D002470:Cell Survival; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004660:Encephalitis / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D004927:Escherichia coli Infections / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases