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ID 17075
file
creator
Kinane, Denis F.
Stathopoulou, Panagiota G.
Zhao, Hongli
Lappin, David F.
Singh, Amar
Eskan, Mehmet A.
Beckers, Simone
Weigel, Sabine
Alpert, Brian
Knudsen, Thomas B.
subject
Toll-like receptors
periodontitis
epithelial cells
tissue culture
disease susceptibility
abstract
The Toll-like receptor (TLR4) is the major sensor for bacterial lipopolysaccharide and its two common co-segregating polymorphisms, Asp299Gly and Thr399Ile, which occur at a frequency of between 6 and 10%, have been associated with infectious diseases, LPS hypo-responsiveness and cardiovascular disease. Porphyromonas gingivalis is a Gram negative bacterium implicated in chronic periodontitis and is a known TLR4 and TLR2 agonist. We obtained two gingival epithelial cell primary cultures from subjects heterozygous for the TLR4 polymorphism Asp299Gly and compared response characteristics with similar cells from patients (four) with the wild type TLR4 genes. Cytokine responses and transcriptome profiles of gingival epithelial cell primary culture cells to TNFα challenge were similar for all primary epithelial cell cultures. P. gingivalis challenge however, gave markedly different responses for Asp299Gly heterozygous and wild-type epithelial cell cultures. The epithelial cells heterozygous for the TLR4 polymorphism Asp299Gly were functionally hypo-responsive, evidenced by differences in BD-2 mRNA expression, mRNA response profile by microarray analysis and by pro-inflammatory and chemokine cytokines at the protein and mRNA level. These findings emphasize variance in human epithelial cell TLRs, linked with Asp299Gly carriage, which results in a hypo-responsive epithelial cell phenotype less susceptible to Gram negative diseases and associated systemic conditions.
journal title
Genes and Immunity
volume
Volume 7
issue
Issue 3
start page
190
end page
200
date of issued
2006-04
publisher
Nature Publishing Group
issn
1466-4879
ncid
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2006 Nature Publishing Group.
relation url
department
Graduate School of Biomedical Science