title: Interleukin 26 suppresses receptor activator of nuclear factor κB ligand induced osteoclastogenesis via down-regulation of nuclear factor of activated T-cells, cytoplasmic 1 and nuclear factor κB activity.
abstract: OBJECTIVE
  IL-26 has been shown to have high expression in RA. However, the effects of IL-26 on bone destruction in RA have not been evaluated. The aim of this study was to investigate the effects and mechanisms of IL-26 on RANK ligand (RANKL)-induced osteoclastogenesis.
  
  
  METHODS
  We treated cells with IL-26 in RANKL-induced oseteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed by pit formation assay and F-actin ring formation. The mechanism of the inhibition was studied by biochemical analyses such as RT-PCR, immunofluorescence staining and immunoblotting. In addition, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
  
  
  RESULTS
  IL-26 inhibited RANKL-induced TRAP-positivemultinucleated cells and inhibited RANKL-induced nuclear factor κB (NF-κB) activation and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) nuclear translocation in RAW264.7 cells. Also, IL-26 significantly inhibited the bone-resorbing activity and F-actin ring formation ability of mature osteoclasts. Moreover, IL-26 suppressed RANKL-induced mitogen-activated protein kinase activation and NFATc1 downstream gene expression.
  
  
  CONCLUSIONS
  We suggest that the inhibitory activity of IL-26 on osteoclastogenesis is via down-regulation of RANKL-induced NF-κB and NFATc1 expression. Our results suggest IL-26 as a possible new remedy against osteolytic bone destruction.
authors.affiliation: Department of Pathology, Tri-Service General Hospital.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Peng
authors.affiliation: Department and Graduate institute of Biology and Anatomy.
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department and Graduate institute of Biology and Anatomy.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department and Graduate institute of Biology and Anatomy.
authors.forename: Gu-Jiun
authors.initials: GJ
authors.lastname: Lin
authors.affiliation: Department and Graduate institute of Biology and Anatomy.|Department of General Surgery, Tri-Service General Hospital.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department and Graduate institute of Biology and Anatomy.
authors.forename: Jia-Fwu
authors.initials: JF
authors.lastname: Shyu
authors.affiliation: Graduate Institute of Life Sciences.|Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.affiliation: Department and Graduate institute of Biology and Anatomy ph870317@ndmctsgh.edu.tw.
authors.forename: Chia-Pi
authors.initials: CP
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000503:physiopathology; D001862:Bone Resorption / Q000503:physiopathology; D015536:Down-Regulation; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D010014:Osteolysis / Q000503:physiopathology; D053245:RANK Ligand / Q000378:metabolism; D000067996:RAW 264.7 Cells
chemical_list: C406767:IL26 protein, human; D007378:Interleukins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: interleukin-26; macrophage; osteoclastogenesis; rheumatoid arthritis