title: Actinobacillus actinomycetemcomitans lipopolysaccharide stimulates collagen phagocytosis by human gingival fibroblasts.
abstract: BACKGROUND
  Collagen phagocytosis by fibroblasts is involved in the intracellular pathway related to collagen breakdown in soft connective tissues. The possible role of lipopolysaccharide (LPS) in regulating this fibroblast function has not been elucidated so we investigated the effect of LPS from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, on collagen phagocytic activity in human gingival fibroblasts and associated regulatory mechanisms.
  
  
  METHODS
  LPS pretreatment stimulated binding of collagen-coated beads to cells and, subsequently, their internalization.
  
  
  RESULTS
  The LPS-activated collagen phagocytic process was enhanced in the presence of the soluble form of CD14 (sCD14) or LPS-binding protein (LBP), while the LPS/LBP treatment activated Akt and induced actin reorganization. Furthermore, these LPS/LBP-induced effects were partially suppressed by adding phosphatidyl-inositol-3 kinase (PI3K) inhibitors.
  
  
  CONCLUSIONS
  These results suggest that A. actinomycetemcomitans LPS disturbs the homeostasis of collagen metabolism within gingival tissue by facilitating collagen phagocytosis by gingival fibroblasts, and serum sCD14 and LBP positively regulate the action of LPS. In addition, the PI3K/Akt signaling is thought to partially mediate the LPS/LBP-stimulated collagen phagocytic pathway, which may be dependent on actin cytoskeletal rearrangement.
authors.affiliation: Department of Periodontology, Showa University School of Dentistry, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Takaki
authors.forename: K
authors.initials: K
authors.lastname: Takano
authors.forename: M
authors.initials: M
authors.lastname: Miyata
authors.forename: Y
authors.initials: Y
authors.lastname: Okamatsu
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Nishihara
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000199:Actins / Q000187:drug effects; D000209:Acute-Phase Proteins / Q000494:pharmacology; D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans; D000730:Androstadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D000077191:Wortmannin; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000199:Actins; D000209:Acute-Phase Proteins; D000730:Androstadienes; D002352:Carrier Proteins; D002867:Chromones; D003094:Collagen; D015638:Cytochalasin D; D004791:Enzyme Inhibitors; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; D000099231:Lipopolysaccharide-Binding Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one