title: Advanced glycation end products upregulate the endoplasmic reticulum stress in human periodontal ligament cells.
abstract: BACKGROUND
  The accumulation of advanced glycation end products (AGEs) appears to be the main factor responsible for modulating periodontal inflammation in diabetes. The aim of this study is to examine the effects of AGEs on inflammation in human periodontal ligament cells and to investigate the mechanism with a specific emphasis on the role of endoplasmic reticulum (ER) stress-induced nuclear factor-kappa B (NF-κB) pathway.
  
  
  METHODS
  Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expressions of ER markers and NF-κB were examined by Western blot analysis. The translocation of NF-κB was observed by immunofluorescence assay. Proinflammatory chemokine production was determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Treatment with AGEs reduced cell viability in a concentration- and time-dependent manner. AGEs induced ER stress, as evidenced by survival molecules, such as glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), and activating transcription factor 6 (ATF-6), and apoptotic molecules, such as CCAAT/enhancer binding protein homologous protein (CHOP) and caspase 12. AGEs upregulated the nucleoprotein expression of NF-κB, enhanced translocation of NF-κB from the cytoplasm to the nucleus, and increased the production of proinflammatory chemokines interleukin-6 and interleukin-8.
  
  
  CONCLUSIONS
  AGEs mediate inflammation of human periodontal ligament cells via the ER stress-induced NF-κB pathway.
authors.affiliation: Department of Stomatology, Hebei University of Science and Technology, Shijiazhuang, Hebei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Xiong
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.forename: Huangqin
authors.initials: H
authors.lastname: Chen
mesh_terms: D051702:Activating Transcription Factor 6 / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D022762:CCAAT-Enhancer-Binding Proteins / Q000187:drug effects; D053454:Caspase 12 / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000187:drug effects; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000187:drug effects; D018836:Inflammation Mediators / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000187:drug effects; D055815:Young Adult; D019892:eIF-2 Kinase / Q000187:drug effects
chemical_list: D051702:Activating Transcription Factor 6; D022762:CCAAT-Enhancer-Binding Proteins; D053454:Caspase 12; D018925:Chemokines; D000091342:Endoplasmic Reticulum Chaperone BiP; D017127:Glycation End Products, Advanced; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C497111:ATF6 protein, human; C508606:CXCL8 protein, human; C497249:DDIT3 protein, human; C000717247:HSPA5 protein, human; C508600:IL6 protein, human; C506444:CASP12 protein, human
keywords: Diabetes mellitus; endoplasmic reticulum stress; glycation end products, advanced; inflammation; nuclear factor-kappa B; periodontal diseases