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ID 114681
Title Alternative
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
Author
Keywords
AGEs
lipocalin2
diabetes mellitus
periodontitis
human oral epithelial cells
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Periodontal Research
ISSN
00223484
16000765
NCID
AA00704381
AA11628616
Publisher
Wiley
Volume
55
Issue
4
Start Page
539
End Page
550
Published Date
2020-03-13
Remark
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。
This is the peer reviewed version of the following article: Kido, R, Hiroshima, Y, Kido, J‐I, et al. Advanced glycation end‐products increase lipocalin 2 expression in human oral epithelial cells. J Periodont Res. 2020; 55: 539– 550, which has been published in final form at https://doi.org/10.1111/jre.12741.
This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3424号
Diploma Number
甲口第462号
Granted Date
2020-04-09
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Institute of Advanced Medical Sciences
Oral Sciences
University Hospital