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Pb 2+ induced IL‐8 gene expression by extracellular signal‐regulated kinases and the transcription factor, activator protein 1, in human gastric carcinoma cells
Author(s) -
Lin YingChi,
Wei PoLi,
Tsai YaoTing,
Wong JhenHong,
Chang CheMai,
Wang JawYuan,
Hou MingFeng,
Lee YiChao,
Chuang HungYi,
Chang WeiChiao
Publication year - 2015
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.21909
Subject(s) - signal transduction , cancer research , activator (genetics) , kinase , carcinogenesis , mapk/erk pathway , biology , microbiology and biotechnology , gene expression , transcription factor , chemokine , chemistry , inflammation , receptor , gene , immunology , biochemistry
Divalent lead (Pb 2+ ) is a common industrial pollutant epidemiologically associated with gastric cancers. Pb 2+ was found to promote tumorigenesis, which may include interleukin (IL)‐8, a pro‐inflammatory chemokine that promotes angiogenesis and tumor metastasis. Given that the gastrointestinal tract is a major route of Pb 2+ exposure, we investigated the ability of Pb 2+ to induce IL‐8 expression in gastric carcinoma cells and its underlying mechanism. At a concentration of 0.1 μM, Pb 2+ induced IL‐8 gene activation in gastric carcinoma AGS cells. Using a IL‐8 promoter‐deletion analysis, transcription factor activator protein 1 (AP‐1) was identified as a necessary component of Pb 2+ ‐induced IL‐8 gene activation. Upregulation of the IL‐8 gene was abrogated by the MEK inhibitor, PD98059, and partially suppressed by the epidermal growth factor receptor inhibitors, AG1478 and PD153035. Furthermore, c‐Jun protein expression was induced in cells treated with Pb 2+ , and overexpression of c‐Jun enhanced Pb 2+ ‐induced IL‐8 activation. Collectively, our findings highlight the pivotal roles of AP‐1 and extracellular signal‐regulated kinase in signal transduction of Pb 2+ ‐induced IL‐8 gene activation. These molecules may be potential therapeutic targets for Pb 2+ ‐related inflammation leading to stomach carcinogenesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 315–322, 2015.