| Febrile-range hyperthermia augments lipopolysaccharide-induced lung injury by a mechanism of enhanced alveolar epithelial apoptosis. | |
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MedLine Citation:
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PMID: 20200273 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fever is common in critically ill patients and is associated with worse clinical outcomes, including increased intensive care unit mortality. In animal models, febrile-range hyperthermia (FRH) worsens acute lung injury, but the mechanisms by which this occurs remain uncertain. We hypothesized that FRH augments the response of the alveolar epithelium to TNF-alpha receptor family signaling. We found that FRH augmented LPS-induced lung injury and increased LPS-induced mortality in mice. At 24 h, animals exposed to hyperthermia and LPS had significant increases in alveolar permeability without changes in inflammatory cells in bronchoalveolar lavage fluid or lung tissue as compared with animals exposed to LPS alone. The increase in alveolar permeability was associated with an increase in alveolar epithelial apoptosis and was attenuated by caspase inhibition with zVAD.fmk. At 48 h, the animals exposed to hyperthermia and LPS had an enhanced lung inflammatory response. In murine lung epithelial cell lines (MLE-15, LA-4) and in primary type II alveolar epithelial cells, FRH enhanced apoptosis in response to TNF-alpha but not Fas ligand. The increase in apoptosis was caspase-8 dependent and associated with suppression of NF-kappaB activity. The FRH-associated NF-kappaB suppression was not associated with persistence of IkappaB-alpha, suggesting that FRH-mediated suppression of NF-kappaB occurs by means other than alteration of IkappaB-alpha kinetics. These data show for the first time that FRH promotes lung injury in part by increasing lung epithelial apoptosis. The enhanced apoptotic response might relate to FRH-mediated suppression of NF-kappaB activity in the alveolar epithelium with a resultant increase in susceptibility to TNF-alpha-mediated cell death. |
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Authors:
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Anne B Lipke; Gustavo Matute-Bello; Raquel Herrero; Kiyoyasu Kurahashi; Venus A Wong; Stephen M Mongovin; Thomas R Martin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-03-03 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-22 Completed Date: 2010-04-27 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3801-13 Citation Subset: AIM; IM |
Affiliation:
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Medical Research Service, VA Puget Sound Medical Center, University of Washington, Seattle, WA 98108, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology* Bronchoalveolar Lavage Fluid / chemistry Epithelial Cells / pathology Fever / immunology, physiopathology* Flow Cytometry In Situ Nick-End Labeling Inflammation / immunology, physiopathology Lipopolysaccharides / immunology, toxicity Lung Injury / immunology, physiopathology* Male Mice Mice, Inbred C57BL NF-kappa B / metabolism Pulmonary Alveoli / immunology, pathology* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Tumor Necrosis Factor-alpha / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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F32 HL096348-01/HL/NHLBI NIH HHS; HL081764/HL/NHLBI NIH HHS; HL083044/HL/NHLBI NIH HHS; HL096348/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lipopolysaccharides; 0/NF-kappa B; 0/Tumor Necrosis Factor-alpha |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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