title: Stimulatory effects of glucose and Porphyromonas gingivalis lipopolysaccharide on the secretion of inflammatory mediators from human macrophages.
abstract: BACKGROUND
  Hyperglycemia is widely considered to be the causal link between diabetes mellitus (DM) and diabetic complications. The purpose of this study is to determine the effects of high glucose in the presence of lipopolysaccharide (LPS) purified from the periodontal pathogen Porphyromonas gingivalis on human macrophages.
  
  
  METHODS
  Macrophages (U937) were treated with various concentrations of P. gingivalis-LPS under normal (5.5 mM) or high (25 mM) glucose conditions. Mitochondrial dehydrogenase activity was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide assay. The levels of inflammatory mediators secreted were determined using the enzyme-linked immunosorbent assay and the competitive enzyme immunoassay. The intracellular calcium chelator was used to examine whether the intracellular calcium was involved. Statistical differences were assessed using a one-way analysis of variance and Tukey multiple-comparison intervals with α = 0.05.
  
  
  RESULTS
  High glucose condition enhanced the mitochondrial dehydrogenase activity in macrophages. P. gingivalis-LPS induced the secretion of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and prostaglandin E(2) (PGE(2)) in a dose-dependent manner both in normal and high glucose conditions. The stimulatory effects by P. gingivalis-LPS were more evident when cells were cultured under high glucose conditions. Changes of intracellular calcium concentration were involved not only in high glucose-induced mitochondrial dehydrogenase activity but also in P. gingivalis-LPS-induced production of IL-6, TNF-α, or PGE(2), especially under the high glucose conditions.
  
  
  CONCLUSIONS
  High glucose appeared to enhance the inflammatory response induced by the periodontal pathogen. The information generated may help to delineate the possible mechanisms by which hyperglycemia compromises the periodontal health of patients with DM.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shan-Ling
authors.initials: SL
authors.lastname: Hung
authors.forename: Nin-Gi
authors.initials: NG
authors.lastname: Lee
authors.forename: Lien-Yu
authors.initials: LY
authors.lastname: Chang
authors.forename: Yen-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lai
mesh_terms: D002118:Calcium / Q000032:analysis; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004396:Coloring Agents; D015232:Dinoprostone / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D008928:Mitochondria / Q000201:enzymology; D010088:Oxidoreductases / Q000032:analysis; D016966:Porphyromonas gingivalis / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D004396:Coloring Agents; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D010088:Oxidoreductases; C022616:thiazolyl blue; D005947:Glucose; D015232:Dinoprostone; D002118:Calcium