title: Effect of high glucose, Porphyromonas gingivalis lipopolysaccharide and advanced glycation end-products on production of interleukin-6/-8 by gingival fibroblasts.
abstract: OBJECTIVE
  It is known that chronic periodontal infection can magnify the cytokine responses in patients with diabetes. Hyperglycemia increases the proinflammatory status, including the levels of advanced glycation end-products (AGEs), in patients with periodontitis. However, whether AGEs have additional effects on the production of those proinflammatory cytokines in diabetic patients with periodontitis is still unknown. To examine in vitro the effect of hyperglycemia and AGEs on the amounts of interleukin (IL)-6 and IL-8 produced in periodontally infected gingiva, human gingival fibroblasts (HGFs) were stimulated with glucose, AGE-modified bovine serum albumin (AGE-BSA) and Porphyromonas gingivalis LPS in the present study.
  
  
  METHODS
  Primary culture of HGFs was incubated with various concentrations of AGE-BSA (0, 50, 100 and 200 μg/mL) and LPS (0, 10, 100 or 1000 ng/mL) at two different glucose concentrations - normal glucose (5 mm) and high glucose (25 mm). The amounts of IL-6 and IL-8 produced by HGFs were evaluated using ELISA. Expression of the AGE receptor on HGFs was determined by flow cytometry.
  
  
  RESULTS
  High glucose stimulated a significant increase in the production of IL-6 and IL-8 by HGFs compared with normal glucose. This enhanced production of IL-6 and IL-8 could also be observed in the presence of LPS and/or AGE-BSA. When both LPS and AGE-BSA were present, especially at high concentrations (≥ 500 μg/mL of LPS and ≥ 25 μg/mL of AGE-BSA), a synergistic effect on IL-8 production was found in the high-glucose condition.
  
  
  CONCLUSIONS
  A synergistic effect of the production of IL-8 could be induced in HGFs with the combination of high glucose, LPS and AGEs.
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.|Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: H-C
authors.initials: HC
authors.lastname: Chiu
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: M M-J
authors.initials: MM
authors.lastname: Fu
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.|Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: T-S
authors.initials: TS
authors.lastname: Yang
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.|Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: E
authors.initials: E
authors.lastname: Fu
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.|Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chiang
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: H-P
authors.initials: HP
authors.lastname: Tu
authors.affiliation: Institutes for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chin
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors.forename: F-G
authors.initials: FG
authors.lastname: Lin
authors.affiliation: Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.|Division of Endocrinology & Metabolism, Taipei-Veteran General Hospital, Taipei, Taiwan.
authors.forename: K-C
authors.initials: KC
authors.lastname: Shih
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D005947:Glucose
keywords: advanced glycation end products; glucose; interleukin-6/-8; lipopolysaccharides