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dc.contributor.authorZuo, Zhenghong
dc.contributor.author左正宏
dc.contributor.authorCai, Tongjian
dc.contributor.authorLi, Jingxia
dc.contributor.authorZhang, Dongyun
dc.contributor.authorYu, Yonghui
dc.contributor.authorHuang, Chuanshu
dc.date.accessioned2013-04-15T07:57:11Z
dc.date.available2013-04-15T07:57:11Z
dc.date.issued2012-04
dc.identifier.citationENVIRONMENTAL HEALTH PERSPECTIVES,2012,12(4):547-553zh_CN
dc.identifier.issn0091-6765
dc.identifier.urihttp://dx.doi.org/10.1289/ehp.1104179
dc.identifier.uriWOS:000302476200025
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/15629
dc.description.abstractBackground: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood. Objectives: We evaluated cyclooxygenase2 (COX 2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells. Methods: We used the luciferase reporter assay and Western blotting to determine COX 2 induction by Cr(VI). We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX 2 induction. Results: We found that Cr(VI) exposure induced COX 2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration and timedependent manner. Deletion of IKK beta [inhibitor of transcription factor NF kappa B (I kappa B) kinase beta; an upstream kinase responsible for nuclear factor kappa B (NF kappa B) activation] or overexpression of TAM67 (a dominantnegative mutant of cJun) dramatically inhibited the COX 2 induction due to Cr(VI), suggesting that both NF kappa B and cJun/AP1 pathways were required for Cr(VI)induced COX 2 expression. Our results show that p65 and cJun are two major components involved in NF.B and AP1 activation, respectively. Moreover, our studies suggest crosstalk between NF.B and cJun/AP1 pathways in cellular response to Cr(VI) exposure for COX 2 induction. Conclusion: We demonstrate for the first time that Cr(VI) is able to induce COX 2 expression via an NF kappa B/cJun/AP1dependent pathway. Our results provide novel insight into the molecular mechanisms linking Cr(VI) exposure to lung inflammation and carcinogenesis.zh_CN
dc.description.sponsorshipNational Institutes of Health (NIH)/National Cancer Institute [CA112557-06, CA119028-05S110]; NIH/National Institute of Environmental Health Sciences [ES012451, ES010344]zh_CN
dc.language.isoenzh_CN
dc.publisherUS DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCEzh_CN
dc.subjectAP-1zh_CN
dc.subjectchromiumzh_CN
dc.subjectc-Junzh_CN
dc.subjectCOX-2zh_CN
dc.subjectNF kappa Bzh_CN
dc.titleHexavalent Chromium Cr(VI) Up-Regulates COX-2 Expression through an NF kappa B/c-Jun/AP-1-Dependent Pathwayzh_CN
dc.typeArticlezh_CN


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