Source:http://linkedlifedata.com/resource/pubmed/id/15944319
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2005-6-9
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| pubmed:abstractText |
Th1/Tc1 inflammation and remodeling responses characterized by tissue atrophy and destruction frequently coexist in human diseases and disorders. However, the mechanisms that are used by Th1/Tc1 cytokines, like IFN-gamma, to induce these responses have not been defined. To elucidate the mechanism(s) of IFN-gamma-induced tissue remodeling and destruction, we characterized the pathway that lung-targeted, transgenic IFN-gamma uses to induce alveolar remodeling in a murine pulmonary emphysema modeling system. In these mice, transgenic IFN-gamma caused epithelial cell DNA injury and apoptosis detectable with TUNEL (Roche) and dual annexin V and propidium iodide staining. These responses were associated with death receptor and mitochondrial apoptosis pathway activation. Importantly, apoptosis inhibition with a caspase inhibitor (N-benzylcarboxy-Val-Ala-Asp-fluoromethyl-ketone) or a null mutation of caspase-3 blocked this DNA injury and apoptosis response and significantly ameliorated IFN-gamma-induced emphysema. These interventions also ameliorated IFN-gamma-induced inflammation and decreased pulmonary protease burden. Selective cathepsin S inhibition and a null mutation of cathepsin S also decreased IFN-gamma-induced DNA injury, apoptosis, emphysema, inflammation, and protease accumulation. These studies demonstrate that cathepsin S-dependent epithelial cell apoptosis is a critical event in the pathogenesis of IFN-gamma-induced alveolar remodeling and emphysema. They also link inflammation, protease/antiprotease alterations, and protease-dependent apoptosis in the pathogenesis of Th1/Tc1 cytokine-induced tissue remodeling and destructive responses.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
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| pubmed:issn |
0022-1767
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| pubmed:author |
pubmed-author:AldousDavidD,
pubmed-author:ChapmanHarold AHA,
pubmed-author:CrothersKristinaK,
pubmed-author:De SanctisGeorge TGT,
pubmed-author:DesanctisGeorgeG,
pubmed-author:EliasJack AJA,
pubmed-author:FlavellRichard ARA,
pubmed-author:GraupeMichaelM,
pubmed-author:HomerRobert JRJ,
pubmed-author:KangMin JongMJ,
pubmed-author:LeeChun GeunCG,
pubmed-author:RabachLesley ALA,
pubmed-author:SchmidtJohn AJA,
pubmed-author:TomP APA,
pubmed-author:UnderwoodStephenS,
pubmed-author:ZhengTaoT,
pubmed-author:ZhuZhouZ
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
174
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
8106-15
|
| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15944319-Animals,
pubmed-meshheading:15944319-Apoptosis,
pubmed-meshheading:15944319-Cathepsins,
pubmed-meshheading:15944319-DNA Damage,
pubmed-meshheading:15944319-Disease Models, Animal,
pubmed-meshheading:15944319-Enzyme Induction,
pubmed-meshheading:15944319-Humans,
pubmed-meshheading:15944319-Inflammation,
pubmed-meshheading:15944319-Interferon-gamma,
pubmed-meshheading:15944319-Lung,
pubmed-meshheading:15944319-Mice,
pubmed-meshheading:15944319-Mice, Inbred C57BL,
pubmed-meshheading:15944319-Mice, Knockout,
pubmed-meshheading:15944319-Mice, Transgenic,
pubmed-meshheading:15944319-Organ Specificity,
pubmed-meshheading:15944319-Pulmonary Alveoli,
pubmed-meshheading:15944319-Pulmonary Emphysema,
pubmed-meshheading:15944319-Respiratory Mucosa,
pubmed-meshheading:15944319-Signal Transduction
|
| pubmed:year |
2005
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| pubmed:articleTitle |
Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema.
|
| pubmed:affiliation |
Department of Internal Medicine, Yale University School of Medicine, Section of Pulmonary and Critical Care Medicine, New Haven, CT 06520, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
|