title: Involvement of HMGB1 and RAGE in IL-1β-induced gingival inflammation.
abstract: OBJECTIVE
  Extracellularly released high mobility group box 1 (HMGB1) protein behaves as a cytokine, promotes inflammation and participates in the pathogenesis of several disorders in peripheral organs. The role of HMGB1 and receptor for advanced glycation end products (RAGE) expressed in gingival inflammatory tissues was explored.
  
  
  METHODS
  Real time PCR was applied to assay HMGB1 and RAGE mRNA expression in gingival epithelial and fibroblast cells induced by interleukin-1β (IL-1β). A highly selective inhibitor of inducible nitric oxide (iNOS) was employed. ELISA was done for measurement of HMGB1 concentrations in cell culture media of gingival epithelial and fibroblast cells. Immunohistochemistry was performed to analyse the expression and sub-cellular localization of HMGB1, together with RAGE, in specimens obtained from patients with chronic inflammation.
  
  
  RESULTS
  A time-dependent response of HMGB1 and RAGE expression in gingival cells to IL-1β induction was observed. IL-1β promotes HMGB1 production in human gingival epithelial cells in a nitric oxide-dependent manner. HMGB1 and RAGE appeared highly expressed in gingival inflammatory tissues.
  
  
  CONCLUSIONS
  These results demonstrate that HMGB1 and RAGE are abundantly expressed in gingiva and promptly released during gingival inflammation. We suggest a role for HMGB1/RAGE/iNOS signalling on inflamed gingival epithelial cells.
authors.affiliation: Department of Comprehensive Dentistry, Kanagawa Dental College, Yokosuka, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ito
authors.forename: Ujjal K
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Toshizo
authors.initials: T
authors.lastname: Toyama
authors.forename: Takenori
authors.initials: T
authors.lastname: Sato
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuda
authors.forename: Harue
authors.initials: H
authors.lastname: Nishikiori
authors.forename: Masaru
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Nobushiro
authors.initials: N
authors.lastname: Hamada
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Arakawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D053583:Interleukin-1beta; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009569:Nitric Oxide