title: Tumor necrosis factor-alpha stimulates gingival epithelial cells to release high mobility-group box 1.
abstract: OBJECTIVE
  High-mobility-group box 1 functions as a late-phase inflammatory mediator. It can be released extracellularly by macrophages and necrotic cells through lipopolysaccharide and tumor necrosis factor-alpha. The objective of this study was to clarify the source of high-mobility-group box 1 in chronic periodontitis tissues and tumor necrosis factor-alpha-stimulated gingival epithelial cells, and subsequently elucidate its inducible inflammatory pathway.
  
  
  METHODS
  Chronic periodontitis and healthy gingival sections were stained for high-mobility-group box 1 by immunohistochemistry and immunofluorescence. The amounts of high-mobility-group box 1 released into the gingival crevicular fluid and supernatants from gingival epithelial cells stimulated by tumor necrosis factor-alpha were examined by western blot. The phosphorylation of mitogen-activated protein kinases (MAPKs) in gingival epithelial cells was also examined.
  
  
  RESULTS
  High-mobility-group box 1 was detected in the cytoplasm and nucleus of gingival epithelial cells with periodontitis. Western blotting revealed a significant increase in high-mobility-group box 1 expression in the gingival crevicular fluid from periodontitis patients. High-mobility-group box 1 production in gingival epithelial cells was increased following stimulation with tumor necrosis factor-alpha. The molecular dialogue between tumor necrosis factor-alpha and gingival epithelial cells involved modulation of the activities of p38MAPK, Jun N-terminal kinase and p44/42. Interestingly, only phosphorylation of p38MAPK contributed to more than half of the signaling initiated by tumor necrosis factor-alpha-elicited high-mobility-group box 1 release.
  
  
  CONCLUSIONS
  High-mobility-group box 1 is continuously released from the gingival epithelial cells modulated by tumor necrosis factor-alpha. These findings imply that high-mobility-group box 1 expression and possibly p38MAPK constitute important features in periodontitis.
authors: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Y
authors: Y
authors: Morimoto
authors: K-I
authors: KI
authors: Kawahara
authors: S
authors: S
authors: Tancharoen
authors: K
authors: K
authors: Kikuchi
authors: T
authors: T
authors: Matsuyama
authors: T
authors: T
authors: Hashiguchi
authors: Y
authors: Y
authors: Izumi
authors: I
authors: I
authors: Maruyama
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002470:Cell Survival; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D025741:HMGA1a Protein / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000032:analysis / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D025741:HMGA1a Protein; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases