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ID 111725
タイトル別表記
カルプロテクチンは、ヒト歯肉線維芽細胞のTLR4を介してIL-6, MCP-1の産生を誘導する
Calprotectin/TLR4 induced induced-Cytokine Production
著者
西川, 泰史 徳島大学大学院口腔科学教育部(口腔科学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Lew, Jung Hwan Tokushima University
キーワード
calprotectin
gingival fibroblasts
periodontitis
cytokine
TLR4
IL-6
MCP-1
資料タイプ
学位論文
抄録
Calprotectin, a heterodimer of S100A8 and S100A9 molecules, is associated with inflammatory diseases such as inflammatory bowel disease. We have reported that calprotectin levels in gingival crevicular fluids of periodontitis patients are significantly higher than in healthy subjects. However, the functions of calprotectin in pathophysiology of periodontitis are still unknown. The aim of this study is to investigate the effects of calprotectin on the productivity of inflammatory cytokines in human gingival fibroblasts(HGFs). The HGFs cell line CRL-2014®(ATCC) were cultured, and total RNAs were collected to examine the expression of TLR2/4 and RAGE mRNA using RT-PCR. After the cells were treated with S100A8, S100A9 and calprotectin, supernatants were collected and the levels of IL-6 and MCP-1 were measured using ELISA methods. To examine the intracellular signals involved in calprotectin-induced cytokine production, several chemical inhibitors were used. Furthermore, after the siRNA-mediated TLR4 down-regulated cells were treated with S100A8, S100A9 and calprotectin, the levels of IL-6 and MCP-1 were also measured. HGFs showed greater expression of TLR4 mRNA, but notTLR2 and RAGE mRNA compared with human oral epithelial cells. Calprotectin increased significantly the production of MCP-1 and IL-6 in HGFs, and the cytokine productions were significantly suppressed in the cells treated with MAPKs, NF-kBand TLR4inhibitors. Furthermore, calprotectin-mediated MCP-1 and IL-6 production were significantly suppressed in TLR4down-regulated cells. Taken together, calprotectin inducesIL-6 and MCP-1 production in HGFs via TLR4 signaling that involves MAPK and NF-kB, resulting in the progression of periodontitis.
掲載誌名
Journal of Cellular Physiology
ISSN
10974652
00219541
cat書誌ID
AA11622711
AA00694856
出版者
Wiley Periodicals
232
7
開始ページ
1862
終了ページ
1871
発行日
2016-12-07
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Yasufumi Nishikawaの学位論文として提出され, 学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3176号
学位記番号
甲口第433号
学位授与年月日
2018-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系
病院