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タイトル別表記
最終糖化産物は口腔上皮細胞におけるLipocain2の発現を増加させる
AGEs increase lipocalin 2 expression
著者
木戸, 理恵 徳島大学大学院口腔科学教育部(口腔科学専攻)
キーワード
AGEs
lipocalin2
diabetes mellitus
periodontitis
human oral epithelial cells
資料タイプ
学位論文
抄録
Background and Objectives: Diabetes mellitus (DM), a risk factor of periodontal diseases, exacerbates the pathological condition of periodontitis. A major factor for DM complications is advanced glycation end-products (AGEs) that accumulate in periodontal tissues and cause inflammatory events. Lipocalin 2 (LCN2) is an antimicrobial peptide and inflammation-related factor, and LCN2 levels increase in DM. In the present study, the effects of AGEs and lipopolysaccharide of Porphyromonas gingivalis (P.g-LPS) on LCN2 expression in human oral epithelial cells (TR146 cells) and the role of secreted LCN2 in periodontitis with DM were investigated.
Material and Methods: TR146 cells were cultured with AGEs (AGE2) and control BSA and cell viability was estimated, or with P.g-LPS. Conditioned medium and cell lysates were prepared from cultures of epithelial cells and used for western blotting and ELISA to analyze LCN2, RAGE, IL-6, MAPK and NF-κB. RNA was isolated from AGE-treated TR146 cells and differentiated HL-60 (D-HL-60) cells and used for quantitative real-time PCR to examine the expression of LCN2 and interleukin-6 (IL-6) mRNAs. RAGE- and LCN2-siRNAs (siRAGE, siLCN2) were transfected into epithelial cells, and AGE-induced LCN2 expression was investigated. D-HL-60 cells were co-cultured with TR146 cells that were transfected with siLCN2 and treated with AGEs, IL-6 mRNA expression in D-HL-60 cells and cell migration were investigated.
Results: AGEs increased the expression levels of LCN2 and IL-6 in oral epithelial cells. siRAGE and a neutralizing antibody for RAGE inhibited AGE-induced LCN2 expression. AGEs stimulated the phosphorylation of ERK, p38 and NF-kB in epithelial cells, and their inhibitors suppressed AGE-induced LCN2 expression. In contrast, P.g-LPS did not show a significant increase on LCN2 level in TR146 cells that expressed toll-like receptor 2. In co-culture experiments, AGE-induced LCN2 inhibited IL-6 mRNA expression in D-HL-60 cells, and LCN2 knockdown in epithelial cells suppressed HL-60 cell migration.
Conclusion: These results suggested that AGEs increase LCN2 expression via RAGE, MAPK, and NF-κB signaling pathways in oral epithelial cells, and secreted LCN2 may influence the pathological condition of periodontitis with DM.
掲載誌名
Journal of Periodontal Research
ISSN
00223484
16000765
cat書誌ID
AA00704381
AA11628616
出版者
Wiley
発行日
2020-03-13
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Rie Kido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。
論文本文は2021-03-13以降公開予定
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
jpn
著者版フラグ
その他
文科省報告番号
甲第3424号
学位記番号
甲口第462号
学位授与年月日
2020-04-09
学位名
博士(歯学)
学位授与機関
徳島大学
部局
先端酵素学研究所
歯学系
病院