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ID 17075
本文ファイル
著者
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.
キーワード
Toll-like receptors
periodontitis
epithelial cells
tissue culture
disease susceptibility
抄録(英)
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.
掲載誌名
Genes and Immunity
7巻
3号
開始ページ
190
終了ページ
200
出版年月日
2006-04
出版者
Nature Publishing Group
ISSN
1466-4879
NCID
出版者DOI
PubMedID
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2006 Nature Publishing Group.
関連情報URL
部局名
医歯薬学総合研究科