Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Listeria monocytogenes invasion of human brain microvascular endothelial cells (BMEC) and its role as a stimulus for endothelial cell activation were studied. Binding and invasion of intact BMEC monolayers were independent of the L. monocytogenes inlAB invasion locus. Cytochalasin D abrogated invasion of BMEC, whereas genistein effected only a 53% decrease in invasion, indicating a requirement for rearrangement of actin microfilaments but less dependence on tyrosine kinase activity. L. monocytogenes stimulated surface expression of E-selectin, ICAM-1, and to a lesser extent, VCAM-1, whereas L. monocytogenes prfA- and Deltahly mutants were severely compromised in this respect. Other experiments showed that BMEC infection stimulated monocyte and neutrophil adhesion and that CD18-mediated binding was the predominant mechanism for neutrophil adhesion to infected BMEC under static conditions. These data suggest that invasion of BMEC is a mechanism for triggering inflammation and leukocyte recruitment into the central nervous system during bacterial meningitis.
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PMID:Listeria monocytogenes infection and activation of human brain microvascular endothelial cells. 981 18

Bacterial meningitis is an acute inflammatory disease of the central nervous system with a mortality rate of up to 30%. Excessive stimulation of the host immune system by bacterial surface components contributes to this devastating outcome. In vitro studies have shown that protein tyrosine kinase inhibitors are highly effective in preventing the release of proinflammatory cytokines induced by pneumococcal cell walls in microglia. In a well-established rat model, intracisternal injection of purified pneumococcal cell walls induced meningitis characterized by increases in the regional cerebral blood flow and intracranial pressure, an influx of leukocytes, and high concentrations of tumor necrosis factor alpha (TNF-alpha) in the cerebrospinal fluid. Compared with the values at the beginning of the experiment, intraperitoneal injection of tyrphostin AG 126 reduced the increases in regional cerebral blood flow (at 6 h, 127% +/- 14% versus 222% +/- 51% of the baseline value; P < 0.05) and intracranial pressure (at 6 h, 0.8 +/- 2.4 versus 5.4 +/- 2.0 mm of Hg; P < 0.05), the influx of leukocytes (at 6 h, 1,336 +/- 737 versus 4,350 +/- 2,182 leukocytes/microl; P < 0.05), and the TNF-alpha concentration (at 6 h, 261 +/- 188 versus 873 +/- 135 pg/microl; P < 0.05). These results demonstrate that inhibition of AG 126-sensitive tyrosine kinase pathways may provide new approaches for preventing excessive inflammation and reducing the increases in blood flow and intracranial pressure in the acute phase of bacterial meningitis.
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PMID:Tyrosine kinase inhibition reduces inflammation in the acute stage of experimental pneumococcal meningitis. 1515 32