Source:http://linkedlifedata.com/resource/pubmed/id/21244753
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2011-1-19
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pubmed:abstractText |
Peroxisome Proliferator-Activated Receptor ?/? belongs to a family of ligand-activated transcription factors. Recent data have clarified its metabolic roles and enhanced the potential role of this receptor as a pharmacological target. Moreover, although its role in acute inflammation remains unclear, being the nuclear receptor PPAR ?/? widely expressed in many tissues, including the vascular endothelium, we assume that the infiltration of PMNs into tissues, a prominent feature in inflammation, may also be related to PPAR ?/?. Mice subjected to intratracheal instillation of bleomycin (BLEO, 1 mg/kg), a glycopeptide produced by the bacterium Streptomyces verticillus, develop lung inflammation and injury characterized by a significant neutrophil infiltration and tissue oedema. Therefore, the aim of this study is to investigate the effects of GW0742, a synthetic high affinity PPAR ?/? agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10 percent DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of: 1) cytokine production; 2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; 3) IkB? degradation and NF-kB nuclear translocation; 4) ERK phosphorylation; 5) stress oxidative by NO formation due to iNOS expression; 6) nitrotyrosine and PAR localization; 7) the degree of apoptosis, evaluated by Bax and Bcl-2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO--instillation in mice.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/GW0742,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR delta,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:issn |
0394-6320
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1033-46
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pubmed:meshHeading |
pubmed-meshheading:21244753-Animals,
pubmed-meshheading:21244753-Apoptosis,
pubmed-meshheading:21244753-Bleomycin,
pubmed-meshheading:21244753-Interleukin-1beta,
pubmed-meshheading:21244753-MAP Kinase Signaling System,
pubmed-meshheading:21244753-Male,
pubmed-meshheading:21244753-Mice,
pubmed-meshheading:21244753-Nitric Oxide,
pubmed-meshheading:21244753-PPAR delta,
pubmed-meshheading:21244753-PPAR-beta,
pubmed-meshheading:21244753-Pneumonia,
pubmed-meshheading:21244753-Thiazoles,
pubmed-meshheading:21244753-Transcription Factor RelA,
pubmed-meshheading:21244753-Tumor Necrosis Factor-alpha
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pubmed:articleTitle |
GW0742, a high affinity PPAR-?/? agonist reduces lung inflammation induced by bleomycin instillation in mice.
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pubmed:affiliation |
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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