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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2011-6-2
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pubmed:abstractText |
We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type, WT) and STAT4(-/-), but not in STAT6(-/-) mice. Moreover, the expression levels of the protein and mRNA of pro-inflammatory cytokines, including TNF-?, IL-1?, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4(-/-), but not STAT6(-/-) mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6(-/-) mice were intact after treatment with cisplatin, whereas those from WT and STAT4(-/-) mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13R?1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Cytotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat6 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1748-7838
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pubmed:author |
pubmed-author:ChungSang-YoungSY,
pubmed-author:JiHye-MinHM,
pubmed-author:KimHyung-JinHJ,
pubmed-author:LeeJeong-HanJH,
pubmed-author:LeeSang-HeonSH,
pubmed-author:LimDavid JDJ,
pubmed-author:LyuAh-RaAR,
pubmed-author:MoonSung-KyunSK,
pubmed-author:OhGi-SuGS,
pubmed-author:ParkChannyC,
pubmed-author:ParkRaekilR,
pubmed-author:ParkSung-JooSJ,
pubmed-author:SoHong-SeobHS,
pubmed-author:SongJehoJ,
pubmed-author:SulJeong-DugJD,
pubmed-author:YouYong-OukYO
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pubmed:issnType |
Electronic
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
944-56
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pubmed:meshHeading |
pubmed-meshheading:21321603-Animals,
pubmed-meshheading:21321603-Antineoplastic Agents,
pubmed-meshheading:21321603-Apoptosis,
pubmed-meshheading:21321603-Cell Line,
pubmed-meshheading:21321603-Cell Survival,
pubmed-meshheading:21321603-Cisplatin,
pubmed-meshheading:21321603-Cochlea,
pubmed-meshheading:21321603-Cytokines,
pubmed-meshheading:21321603-Cytotoxins,
pubmed-meshheading:21321603-Evoked Potentials, Auditory, Brain Stem,
pubmed-meshheading:21321603-Genes, Reporter,
pubmed-meshheading:21321603-Hair Cells, Auditory,
pubmed-meshheading:21321603-Hearing Loss,
pubmed-meshheading:21321603-Luciferases,
pubmed-meshheading:21321603-Mice,
pubmed-meshheading:21321603-Mice, Inbred BALB C,
pubmed-meshheading:21321603-Mice, Knockout,
pubmed-meshheading:21321603-NF-kappa B,
pubmed-meshheading:21321603-Phosphorylation,
pubmed-meshheading:21321603-Promoter Regions, Genetic,
pubmed-meshheading:21321603-RNA Interference,
pubmed-meshheading:21321603-STAT4 Transcription Factor,
pubmed-meshheading:21321603-STAT6 Transcription Factor,
pubmed-meshheading:21321603-Signal Transduction,
pubmed-meshheading:21321603-Transcription, Genetic
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pubmed:year |
2011
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pubmed:articleTitle |
Cisplatin ototoxicity involves cytokines and STAT6 signaling network.
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pubmed:affiliation |
Vestibulocochlear Research Center & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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