Source:http://linkedlifedata.com/resource/pubmed/id/19892012
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2010-2-3
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| pubmed:abstractText |
Exposure to cigarette smoke extract (CSE) leads to airway and lung inflammation through an oxidant-antioxidant imbalance. Cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) have been shown to play critical roles in respiratory inflammation. Here, we show that COX-2/PGE(2)/IL-6 induction is dependent on Toll-like receptor 4 (TLR4)/NADPH oxidase signaling in human tracheal smooth muscle cells (HTSMCs). CSE induced COX-2 expression in vitro in HTSMCs and in vivo in the airways of mice. CSE also directly caused an increase in TLR4. Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65. CSE-induced leukocyte numbers in BAL fluid were also reduced by pretreatment with these inhibitors. Furthermore, CSE induced p47(phox) translocation and TLR4/MyD88/TRAF6 and c-Src/p47(phox) complex formation. We found that PGE(2) enhanced IL-6 production in HTSMCs and leukocyte count in BAL fluid. In addition, treatment with nicotine could induce COX-2, PGE(2), and IL-6 generation in in vivo and in vitro studies. These results demonstrate that CSE-induced ROS generation was mediated through the TLR4/MyD88/TRAF6/c-Src/NADPH oxidase pathway, in turn initiated the activation of MAPKs and NF-kappaB, and ultimately induced COX-2/PGE(2)/IL-6-dependent airway inflammation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Nicotine,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
1873-4596
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2009 Elsevier Inc. All rights reserved.
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
48
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
240-54
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| pubmed:meshHeading |
pubmed-meshheading:19892012-Animals,
pubmed-meshheading:19892012-Cells, Cultured,
pubmed-meshheading:19892012-Cyclooxygenase 2,
pubmed-meshheading:19892012-Dinoprostone,
pubmed-meshheading:19892012-Enzyme Activation,
pubmed-meshheading:19892012-Humans,
pubmed-meshheading:19892012-Interleukin-6,
pubmed-meshheading:19892012-Male,
pubmed-meshheading:19892012-Mice,
pubmed-meshheading:19892012-Mice, Inbred ICR,
pubmed-meshheading:19892012-Myocytes, Smooth Muscle,
pubmed-meshheading:19892012-NADPH Oxidase,
pubmed-meshheading:19892012-Nicotine,
pubmed-meshheading:19892012-Pneumonia,
pubmed-meshheading:19892012-RNA, Small Interfering,
pubmed-meshheading:19892012-Signal Transduction,
pubmed-meshheading:19892012-Smoking,
pubmed-meshheading:19892012-Toll-Like Receptor 4
|
| pubmed:year |
2010
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| pubmed:articleTitle |
Induction of COX-2/PGE(2)/IL-6 is crucial for cigarette smoke extract-induced airway inflammation: Role of TLR4-dependent NADPH oxidase activation.
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| pubmed:affiliation |
Department of Anesthetics, Chang Gung Memorial Hospital, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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