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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2004-1-21
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:BlackwellTimothy STS,
pubmed-author:ChengDong-shengDS,
pubmed-author:ChristmanJohn WJW,
pubmed-author:ContagChristopher HCH,
pubmed-author:HanJ-HJH,
pubmed-author:HollandSteven MSM,
pubmed-author:JansenE DucoED,
pubmed-author:KernodleDouglas SDS,
pubmed-author:SadikotRuxana TRT,
pubmed-author:SegalBrahm HBH,
pubmed-author:YullFiona EFE,
pubmed-author:ZengHengH
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
172
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1801-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:14734763-Animals,
pubmed-meshheading:14734763-Cells, Cultured,
pubmed-meshheading:14734763-Dose-Response Relationship, Immunologic,
pubmed-meshheading:14734763-Immunity, Innate,
pubmed-meshheading:14734763-Lung,
pubmed-meshheading:14734763-Macrophages,
pubmed-meshheading:14734763-Membrane Glycoproteins,
pubmed-meshheading:14734763-Mice,
pubmed-meshheading:14734763-Mice, Inbred C3H,
pubmed-meshheading:14734763-Mice, Inbred C57BL,
pubmed-meshheading:14734763-Mice, Inbred DBA,
pubmed-meshheading:14734763-Mice, Transgenic,
pubmed-meshheading:14734763-NADPH Oxidase,
pubmed-meshheading:14734763-NF-kappa B,
pubmed-meshheading:14734763-Neutrophil Infiltration,
pubmed-meshheading:14734763-Phosphoproteins,
pubmed-meshheading:14734763-Pneumonia, Bacterial,
pubmed-meshheading:14734763-Pseudomonas Infections,
pubmed-meshheading:14734763-Receptors, Cell Surface,
pubmed-meshheading:14734763-Signal Transduction,
pubmed-meshheading:14734763-Toll-Like Receptors
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pubmed:year |
2004
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pubmed:articleTitle |
p47phox deficiency impairs NF-kappa B activation and host defense in Pseudomonas pneumonia.
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pubmed:affiliation |
Department of Veterans Affairs and Division of Allergy, Pulmonary and Critical Care, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. ruxana.sadikot@Vanderbilt.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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