Abstract
TNF is a marker of disease activity in bacterial meningitis. To investigate TNF modulation by Toll-like receptor-2 (TLR2), we studied temporal and anatomical expression patterns of TLR2 and TNF in a pneumococcal meningitis model in wild type (wt) and TLR2(-/-) mice. We show by in situ hybridization that transcripts of TLR2 and of the comolecules CD14, MD-2, TLR1/6 strongly increased and colocalized with TNF in CD45-positive infiltrating cells in the ventricles, corpus callosum and the meninges. TNF gene and protein expression was stronger in TLR2(-/-) than wt brains and associated with increased IkappaB expression suggesting that TLR2 is controlling inflammation via TNF regulation.
MeSH terms
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Analysis of Variance
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Animals
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Blotting, Northern / methods
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Blotting, Western / methods
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Brain / metabolism*
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Brain / microbiology
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Brain / pathology
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Disease Models, Animal
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Enzyme-Linked Immunosorbent Assay / methods
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Gene Expression Regulation / physiology*
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I-kappa B Proteins / genetics
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I-kappa B Proteins / metabolism
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Immunohistochemistry / methods
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In Situ Hybridization / methods
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Leukocytes / metabolism
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Lipopolysaccharide Receptors / metabolism
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Listeria monocytogenes / pathogenicity
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Lymphocyte Antigen 96 / metabolism
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Meningitis, Pneumococcal / metabolism*
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Meningitis, Pneumococcal / microbiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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RNA, Messenger / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Streptococcus pneumoniae / pathogenicity
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Time Factors
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Toll-Like Receptor 2 / deficiency*
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Toll-Like Receptors / genetics
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Toll-Like Receptors / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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I kappa B beta protein
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I-kappa B Proteins
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Lipopolysaccharide Receptors
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Lymphocyte Antigen 96
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RNA, Messenger
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Tlr11 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha
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Interleukin-10