These authors contributed equally to this work.
Pb2+ induced IL-8 gene expression by extracellular signal-regulated kinases and the transcription factor, activator protein 1, in human gastric carcinoma cells
Article first published online: 16 SEP 2013
Copyright © 2013 Wiley Periodicals, Inc.
How to Cite
Lin, Y.-C., Wei, P.-L., Tsai, Y.-T., Wong, J.-H., Chang, C.-M., Wang, J.-Y., Hou, M.-F., Lee, Y.-C., Chuang, H.-Y. and Chang, W.-C. (2013), Pb2+ induced IL-8 gene expression by extracellular signal-regulated kinases and the transcription factor, activator protein 1, in human gastric carcinoma cells. Environ. Toxicol.. doi: 10.1002/tox.21909
- Article first published online: 16 SEP 2013
- Manuscript Accepted: 28 AUG 2013
- Manuscript Revised: 24 AUG 2013
- Manuscript Received: 21 MAY 2013
- Department of Health, Executive Yuan, R.O.C. (Taiwan). Grant Number: DOH102-TD-C-111-002
- National Science Council, Taiwan. Grant Number: NSC101-2320-B-038-029-MY3
- Cancer Center, Kaohsiung Medical University Hospital
Divalent lead (Pb2+) is a common industrial pollutant epidemiologically associated with gastric cancers. Pb2+ 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 Pb2+ exposure, we investigated the ability of Pb2+ to induce IL-8 expression in gastric carcinoma cells and its underlying mechanism. At a concentration of 0.1 μM, Pb2+ 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 Pb2+-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 Pb2+, and overexpression of c-Jun enhanced Pb2+-induced IL-8 activation. Collectively, our findings highlight the pivotal roles of AP-1 and extracellular signal-regulated kinase in signal transduction of Pb2+-induced IL-8 gene activation. These molecules may be potential therapeutic targets for Pb2+-related inflammation leading to stomach carcinogenesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.