title: Mobilization of TLR4 Into Lipid Rafts by Aggregatibacter Actinomycetemcomitans in Gingival Epithelial Cells.
abstract: BACKGROUND
  An investigation of the mechanisms underlying the production of inflammatory cytokines through the stimulation of microorganisms on gingival epithelial cells may provide insights into the pathogenesis of the initiation of periodontitis. Lipid rafts, microdomains in the cell membrane, include a large number of receptors, and are centrally involved in signal transduction. We herein examined the involvement of lipid rafts in the expression of interleukin (IL-6) and IL-8 in gingival epithelial cells stimulated by periodontal pathogens.
  
  
  METHODS
  OBA9, a human gingival cell line, was stimulated by Aggregatibacter actinomycetemcomitans or tumor necrosis factor (TNF)-α in the presence of methyl-β-cyclodextrin (MβCD).
  
  
  RESULTS
  A. actinomycetemcomitans or TNF-α increased IL-8 and IL-6 mRNA levels, and promoted the phosphorylation of ERK and p38 MAP kinase in OBA9. The pretreatment with MβCD abolished increases in IL-6 and IL-8 mRNA levels and the phosphorylation induced by A. actinomycetemcomitans, but did not suppress the response induced by TNF-α. The transfection of TLR4 inhibited A. actinomycetemcomitans-induced increases in IL-8 and IL-6 mRNA levels. Confocal microscopy revealed that MβCD inhibited the mobilization of TLR4 into lipid rafts.
  
  
  CONCLUSIONS
  The mobilization of TLR4 into lipid rafts is involved in the expression of inflammatory cytokines and phosphorylation of MAP kinase in human gingival epithelial cells stimulated by A. actinomycetemcomitans.
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical &amp; Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Imai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ouhara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000254:growth & development* / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000648:ultrastructure; D005786:Gene Expression Regulation; D005881:Gingiva / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D054884:Host-Pathogen Interactions; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D021962:Membrane Microdomains / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases