Interferon-γ-Induced Nitric Oxide Synthase-2 Contributes to Blood/Brain Barrier Dysfunction and Acute Mortality in Experimental Streptococcus pneumoniae Meningitis
作者： Belinda Yau , Andrew J. Mitchell , Lay Khoon Too , Helen J. Ball , Nicholas H. Hunt
关键词:
摘要: The proinflammatory cytokine interferon-gamma (IFNγ) recently was shown to play a crucial role in experimental pneumococcal meningitis (PM) pathogenesis, and we aimed this study investigate IFNγ-driven nitric oxide synthase-2 (NOS2)-mediated pathogenesis of murine PM. We demonstrate that costimulation toll-like receptors IFNγ synergistic for NOS2 expression cultured microglia. Using an PM model, wild-type mice treated with anti-IFNγ antibody, as well gene knockout (GKO) mice, were inoculated intracerebroventricularly 10(3) colony-forming units Streptococcus pneumoniae (WU2 strain). Mice monitored daily during 200-h disease course assess survival rate blood-brain barrier (BBB) permeability measured at 48 h. deficiency protective PM, approximate 3-fold increase rates both antibody-treated GKO compared controls (P < 0.01). At 48 h postinoculation, brain NOS2 mRNA significantly increased IFNγ-dependent manner. Mortality delayed (P < 0.01), BBB dysfunction reduced by 54% abolished GKO. These data suggest the contributes breakdown early mortality
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