Skip Navigation


ToxSci Advance Access originally published online on April 11, 2006
Toxicological Sciences 2006 92(1):311-320; doi:10.1093/toxsci/kfj194
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
92/1/311    most recent
kfj194v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (4)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Eum, S. Y.
Right arrow Articles by Toborek, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eum, S. Y.
Right arrow Articles by Toborek, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

c-Src Is the Primary Signaling Mediator of Polychlorinated Biphenyl–Induced Interleukin-8 Expression in a Human Microvascular Endothelial Cell Line

Sung Yong Eum*, Geun Bae Rha*, Bernhard Hennig{dagger} and Michal Toborek*,1

* Molecular Neuroscience and Vascular Biology Laboratory, Department of Surgery and {dagger} College of Agriculture, University of Kentucky, Lexington, Kentucky 40536

Received January 6, 2006; accepted March 29, 2006

Interleukin-8/CXCL8 (IL-8) is a prominent factor that modulates endothelial cell proliferation, migration, and angiogenesis. Therefore, the present study focused on the regulatory mechanisms of IL-8 expression induced by environmental pollutants such as polychlorinated biphenyls (PCBs). Treatment of human microvascular endothelial cells (HMECs) with specific PCB congener, 2,2',4,6,6'-pentachlorobiphenyl (PCB 104), dose dependently increased levels of IL-8 mRNA and secreted protein. IL-8–neutralizing antibody inhibited migration of endothelial cells stimulated by conditioned media derived from PCB 104–treated HMECs. Site-directed mutagenesis of the IL-8 promoter– and DNA-binding assays revealed that activator protein 1 (AP-1) and nuclear factor {kappa}B (NF-{kappa}B) sites are required for PCB 104–induced IL-8 transcription. Most importantly, pharmacological inhibition of Src kinase activity or overexpression of dominant-negative c-src in HMECs resulted in a significant decrease in IL-8 expression and promoter activity. In contrast, ectopic expression of activated c-Src markedly increased promoter activity of IL-8. These stimulatory effects of dominant-positive c-src were abrogated by mutagenesis of AP-1– and NF-{kappa}B–binding sites in the IL-8 promoter.

Key Words: IL-8; endothelial cells; c-Src; AP-1; NF-{kappa}B; angiogenesis; PCB.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.