title: Secreted proteins from Neisseria meningitidis mediate differential human gene expression and immune activation.
abstract: Meningococcal secreted proteins (MSPs) have been poorly characterized. We hypothesized that MSPs play essential roles in host--bacterial interactions and in the pathogenesis of disease. In order to test this, we examined differential host gene expression in human meningeal-derived cells, in response to endotoxin-depleted MSPs compared to live bacteria. Using expression arrays, upregulated expression of several pro-inflammatory and apoptosis-related genes was found to be induced by MSPs. The transcription and translation of representative genes was confirmed by using various methods. Increased interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) gene transcription was confirmed using real-time PCR. Upregulated IL-8, IL-6, ICAM-1 and COX-2 protein expression were confirmed by ELISA, flow cytometry or Western immunoblots. Furthermore, exposure of cells to MSPs or live meningococci induced a small significant resistance effect to staurosporine-induced apoptosis. Secreted meningococcal virulence factors are therefore important in inducing host inflammatory responses and resistance to apoptosis, and they are worthy of extensive investigation.
authors.affiliation: Molecular Bacteriology and Immunology Group, Division of Microbiology and Infectious Diseases, University Hospital, Nottingham, NG7 2UH, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Robinson
authors.forename: Maria
authors.initials: M
authors.lastname: Taraktsoglou
authors.forename: Kherie S J
authors.initials: KS
authors.lastname: Rowe
authors.forename: Karl G
authors.initials: KG
authors.lastname: Wooldridge
authors.forename: Dlawer A A
authors.initials: DA
authors.lastname: Ala'Aldeen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001426:Bacterial Proteins / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008565:Membrane Proteins; D008578:Meninges / Q000166:cytology; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009345:Neisseria meningitidis / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D019311:Staurosporine / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C023023:lipid-linked oligosaccharides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019311:Staurosporine