Source:http://linkedlifedata.com/resource/pubmed/id/21745554
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2011-8-29
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| pubmed:abstractText |
Alveolar type II epithelial (AEII) cells regulate lung inflammatory response and, simultaneously, they are a target of environmental carcinogenic factors. We employed an in vitro model of rat AEII cells, the RLE-6TN cell line, in order to analyze the interactive effects of tumor necrosis factor-? (TNF-?), a cytokine which plays a key role in the initiation of inflammatory responses in the lung, and benzo[a]pyrene (BaP), a highly carcinogenic polycyclic aromatic hydrocarbon. TNF-? strongly augmented the formation of stable BaP diol epoxide-DNA adducts in AEII cells, which was associated with enhanced p53-Ser15 phosphorylation and decreased cell survival. The increased genotoxicity of BaP was associated with altered expression of cytochrome P450 (CYP) enzymes involved in its bioactivation, a simultaneous suppression of CYP1A1 and enhancement of CYP1B1 expression. Importantly, BaP and TNF-? acted synergistically to upregulate key inflammatory regulators in AEII cells, including the expression of inducible NO synthase and cyclooxygenase-2 (COX-2), and enhanced prostaglandin E2 production and expression of proinflammatory cytokines, such as TNF-?, interleukin-1? and interleukin-6. We observed that BaP and TNF-? together strongly activated p38 kinase, a principal regulator of inflammatory response. SB202190, a specific p38 inhibitor, prevented induction of both COX-2 and proinflammatory cytokines, thus confirming that p38 activity was crucial for the observed inflammatory reaction. Taken together, our data demonstrated, for the first time, that a proinflammatory cytokine and an environmental PAH may interact to potentiate both DNA damage and the inflammatory response in AEII cells, which may occur through coordinated upregulation of p38 activity.
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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/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, Environmental,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 CYP1B1,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1879-3169
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:day |
10
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| pubmed:volume |
206
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
121-9
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| pubmed:meshHeading |
pubmed-meshheading:21745554-Animals,
pubmed-meshheading:21745554-Apoptosis,
pubmed-meshheading:21745554-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:21745554-Benzo(a)pyrene,
pubmed-meshheading:21745554-Carcinogens, Environmental,
pubmed-meshheading:21745554-Cell Line,
pubmed-meshheading:21745554-Cell Proliferation,
pubmed-meshheading:21745554-Cytochrome P-450 CYP1A1,
pubmed-meshheading:21745554-DNA Adducts,
pubmed-meshheading:21745554-Enzyme Activation,
pubmed-meshheading:21745554-Gene Expression Regulation,
pubmed-meshheading:21745554-Inflammation Mediators,
pubmed-meshheading:21745554-Mutagens,
pubmed-meshheading:21745554-Phosphorylation,
pubmed-meshheading:21745554-Pneumocytes,
pubmed-meshheading:21745554-Protein Kinase Inhibitors,
pubmed-meshheading:21745554-Protein Processing, Post-Translational,
pubmed-meshheading:21745554-RNA, Messenger,
pubmed-meshheading:21745554-Rats,
pubmed-meshheading:21745554-Tumor Necrosis Factor-alpha,
pubmed-meshheading:21745554-Tumor Suppressor Protein p53,
pubmed-meshheading:21745554-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2011
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| pubmed:articleTitle |
Benzo[a]pyrene and tumor necrosis factor-? coordinately increase genotoxic damage and the production of proinflammatory mediators in alveolar epithelial type II cells.
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| pubmed:affiliation |
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, Brno, Czech Republic.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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