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      1. Author :
        Sadikot, Ruxana T; Zeng, Heng; Yull, Fiona E; Li, Bo; Cheng, Dong-sheng; Kernodle, Douglas S; Jansen, E Duco; Contag, Christopher H; Segal, Brahm H; Holland, Steven M; Blackwell, Timothy S; Christman, John W
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        Journal of immunology (Baltimore, Md.: 1950)
      6. Products :
      7. Volume :
        172
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Cells, Cultured; Dose-Response Relationship, Immunologic; Immunity, Innate; Lung; Macrophages; Membrane Glycoproteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; NADPH Oxidase; Neutrophil Infiltration; NF-kappa B; Phosphoproteins; Pneumonia, Bacterial; Pseudomonas Infections; Receptors, Cell Surface; Signal Transduction; Toll-Like Receptors; Xen5
      12. Abstract :
        We examined the role of redox signaling generated by NADPH oxidase in activation of NF-kappaB and host defense against Pseudomonas aeruginosa pneumonia. Using mice with an NF-kappaB-driven luciferase reporter construct (HIV-LTR/luciferase (HLL)), we found that intratracheal administration of P. aeruginosa resulted in a dose-dependent neutrophilic influx and activation of NF-kappaB. To determine the effects of reactive oxygen species generated by the NADPH oxidase system on activation of NF-kappaB, we crossbred mice deficient in p47(phox) with NF-kappaB reporter mice (p47(phox-/-)HLL). These p47(phox-/-)HLL mice were unable to activate NF-kappaB to the same degree as HLL mice with intact NADPH oxidase following P. aeruginosa infection. In addition, lung TNF-alpha levels were significantly lower in p47(phox-/-)HLL mice compared with HLL mice. Bacterial clearance was impaired in p47(phox-/-)HLL mice. In vitro studies using bone marrow-derived macrophages showed that Toll-like receptor 4 was necessary for NF-kappaB activation following treatment with P. aeruginosa. Additional studies with macrophages from p47(phox-/-) mice confirmed that redox signaling was necessary for maximal Toll-like receptor 4-dependent NF-kappaB activation in this model. These data indicate that the NADPH oxidase-dependent respiratory burst stimulated by Pseudomonas infection contributes to host defense by modulating redox-dependent signaling through the NF-kappaB pathway.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/14734763
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9999
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