title: Interleukin-12 Induces Receptor Activator of Nuclear Factor-Kappa B Ligand Expression by Human Periodontal Ligament Cells.
abstract: Increased level of proinflammatory cytokine interleukin (IL)-12 correlates with the severity of periodontitis. Yet, a possible role of IL-12 in periodontal disease has not been clarified. The aim of this study is to investigate whether IL-12 affects expression of receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL), a potent osteoclast-stimulating factor, by human periodontal ligament (hPDL) cells.
  
  
  
  To determine the effect of IL-12, hPDL cells were incubated with recombinant human IL-12 (p70) in a dose- (0 to 10 ng/mL) and time-dependent manner. Expression of RANKL was evaluated at mRNA and protein levels. Underlying signaling pathways of IL-12 were determined by using specific inhibitors.
  
  
  
  Under the influence of IL-12, hPDL cells expressed significantly higher levels of RANKL. Expression was mediated by signal transducer and activator of transcription 4 and NF-κB signaling pathways. Conditioned medium of IL-12-incubated cells proved to contain molecule(s) that induced RANKL expression. Addition of suramin (G protein-coupled receptor inhibitor) and ethylene glycol tetraacetic acid (calcium chelator) suggested existence of intermediate molecule(s) that could activate heterotrimeric G protein signaling in a calcium-dependent pathway.
  
  
  
  Expression of RANKL by hPDL cells significantly increased after IL-12 treatment. Therefore, this study supports a close interrelationship between immune and skeletal systems and suggests an osteolytic role of IL-12 in pathogenesis of periodontal disease.
authors.affiliation: Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Benjar
authors.initials: B
authors.lastname: Issaranggun Na Ayuthaya
authors.affiliation: Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.|Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.|Research Institute MOVE, VU University Amsterdam.
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
authors.affiliation: Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.|Department of Anatomy, Faculty of Dentistry, Chulalongkorn University.
authors.forename: Prasit
authors.initials: P
authors.lastname: Pavasant
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism; D010510:Periodontal Diseases / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053707:Receptors, Interleukin-12; C505688:TNFSF11 protein, human; D018664:Interleukin-12
keywords: Bone remodeling; RANK ligand; bone resorption; interleukin-12 periodontitis