Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399Ile are hypo-responsive to Porphyromonas gingivalis

Genes and Immunity 7 巻 3 号 190-200 頁 2006-04 発行
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タイトル ( eng )
Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399Ile are hypo-responsive to Porphyromonas gingivalis
作成者
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.
収録物名
Genes and Immunity
7
3
開始ページ 190
終了ページ 200
抄録
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.
著者キーワード
Toll-like receptors
periodontitis
epithelial cells
tissue culture
disease susceptibility
言語
英語
資源タイプ 学術雑誌論文
出版者
Nature Publishing Group
発行日 2006-04
権利情報
Copyright (c) 2006 Nature Publishing Group.
出版タイプ Author’s Original(十分な品質であるとして、著者から正式な査読に提出される版)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 1466-4879
[DOI] 10.1038/sj.gene.6364282
[PMID] 16437123
[NCID] AA11474931
[DOI] http://dx.doi.org/10.1038/sj.gene.6364282