Skip Navigation



Glycobiology Advance Access published online on November 29, 2005
Glycobiology, doi:10.1093/glycob/cwj061
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
16/3/221    most recent
cwj061v1
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 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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Smith, M. F.
Right arrow Articles by Comeau, L. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, M. F., Jr.
Right arrow Articles by Comeau, L. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.
Received August 11, 2005
Revised November 9, 2005
Accepted November 13, 2005

Article

Helicobacter Pylori and Toll-Like Receptor Agonists Induce Syndecan-4 Expression in an NF-{kappa}B-Dependent Manner

Michael F. Smith Jr. 1 *, Jennifer Novotny 1, Virginia S. Carl 1, and Laurey D. Comeau 1

1 University of Virginia Health System, Departments of Medicine, Digestive Health Center of Excellence and Microbiology, Charlottesville, VA USA

* To whom correspondence should be addressed.
Michael F. Smith Jr., E-mail: mfs3k{at}virginia.edu


  Abstract

The syndecans are a family of transmembrane heparan sulfate proteoglycans that have been implicated in a wide variety of biological functions including the regulation of growth factor signaling, adhesion, tumorigenesis, and inflammation. In the current studies we examined the regulation of syndecan-4 gene expression in gastric epithelial cells and macrophages in response to infection with live Helicobacter pylori and purified Toll-like receptor (TLR) agonists. H. pylori, PAM3CSK4 (a TLR2 agonist) and E. coli flagellin (a TLR5 agonist) all induced the rapid expression of syndecan-4 mRNA in MKN45 gastric epithelial cells. Similarly, LPS (a TLR4 agonist) also induced the expression of syndecan-4 in macrophages. The H. pylori- and TLRinduced increase in syndecan-4 mRNA was blocked by the proteosome inhibitor MG-132 suggesting a role for NF-{kappa}B in the regulation of syndecan-4 gene expression. An 895-bp fragment of the human syndecan-4 promoter was cloned upstream of the luciferase reporter. When transfected into MKN45 cells, the activity of this promoter was inducible by H. pylori and TLR agonists. Inducible activity of the syndecan-4 promoter was blocked by cotransfection with a dominant negative I{kappa}B{alpha} expression plasmid. Electrophoretic mobility shift assays (EMSA) demonstrated the presence of a highly conserved NF-{kappa}B-binding site. Mutation of this site within the context of the full length syndecan-4 promoter resulted in a complete loss of responsiveness to H. pylori and TLR agonists. These results thus demonstrate that the response of the syndecan-4 gene to infectious agents, or their products, is a direct result of NF-{kappa}B binding to the promoter and induction of de novo transcription.

Keywords: Helicobacter/syndecan/heparan sulfate/Toll-like receptor/NF-KappaB.
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.