title: The role of lipopolysaccharide in infectious bone resorption of periapical lesion.
abstract: BACKGROUND
  The role of lipopolysaccharide (LPS) in periapical lesion-induced bone resorption was investigated. Polymyxin B (PMB), a specific inhibitor of LPS, was evaluated to treat the apical lesion.
  
  
  METHODS
  Lipopolysaccharide isolated from two common endodontic pathogens, Fusobacterium nucleatum and Porphyromonas endodontalis, stimulated mouse macrophage (J774) to release interleukin-1alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) in a time-dependent manner.
  
  
  RESULTS
  Combination of LPS further enhanced the stimulation. PMB inhibited these effects significantly. LPS also stimulated matrix metalloproteinase-1 (MMP-1) gene expression in J774, whereas anti-IL-1 alpha and anti-TNF-alpha antibodies, as well as PMB, diminished this effect. A disease model of periapical lesion was established in Wistar rat. Administration of PMB reduced the extent of lesion-associated bone resorption by 76% to approximately 80%, and simultaneously reduced the numbers of MMP-1-producing macrophages.
  
  
  CONCLUSIONS
  It is suggested that LPS released from the infected root canal triggers the synthesis of IL-1 alpha and TNF-alpha from macrophages. These pro-inflammatory cytokines up-regulate the production of MMP-1 by macrophages to promote periapical bone resorption.
authors.affiliation: School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hong
authors.forename: Sze-Kwan
authors.initials: SK
authors.lastname: Lin
authors.forename: Sang-Heng
authors.initials: SH
authors.lastname: Kok
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Cheng
authors.forename: Ming-Shu
authors.initials: MS
authors.lastname: Lee
authors.forename: Tong-Mei
authors.initials: TM
authors.lastname: Wang
authors.forename: Chuan-Shuo
authors.initials: CS
authors.lastname: Chen
authors.forename: Li-Deh
authors.initials: LD
authors.lastname: Lin
authors.forename: Juo-Song
authors.initials: JS
authors.lastname: Wang
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000382:microbiology*; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016967:Fusobacterium nucleatum / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism; D010485:Periapical Periodontitis / Q000188:drug therapy / Q000382:microbiology*; D011112:Polymyxin B / Q000494:pharmacology* / Q000627:therapeutic use; D045202:Porphyromonas endodontalis / Q000472:pathogenicity; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1; D011112:Polymyxin B