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ID 111725
Title Alternative
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
Author
Lew, Jung Hwan Tokushima University
Keywords
calprotectin
gingival fibroblasts
periodontitis
cytokine
TLR4
IL-6
MCP-1
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Cellular Physiology
ISSN
10974652
00219541
NCID
AA11622711
AA00694856
Publisher
Wiley Periodicals
Volume
232
Issue
7
Start Page
1862
End Page
1871
Published Date
2016-12-07
Remark
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3176号
Diploma Number
甲口第433号
Granted Date
2018-03-23
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Oral Sciences
University Hospital