title: Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by IL-17 through PI3-kinase-, NF-kappaB- and p38 MAPK-dependent signalling pathways.
abstract: OBJECTIVE
  To investigate the expression of interleukin (IL)-23p19 in human rheumatoid arthritis (RA) synovial fibroblasts and its up-regulation by IL-17 stimulation, and to define the signal pathways involved in the regulation of IL-23p19 expression in RA synovial fibroblasts.
  
  
  METHODS
  Synovial fluid (SF) and serum levels of IL-23p19 in RA were determined by enzyme-linked immunosorbent assays. The levels of IL-23p19 mRNA and protein were measured after the RA synovial fibroblasts were treated with recombinant human IL-17 and various inhibitors of intracellular signal pathway molecules using reverse transcription (RT) polymerase chain reaction (PCR), real-time PCR and western blotting.
  
  
  RESULTS
  Levels of IL-23p19 in the sera and SF were much higher in RA patients than in osteoarthritis patients or healthy controls. The expression of IL-23p19 mRNA and protein was enhanced in RA synovial fibroblasts by IL-17 stimulation. Such effects of IL-17 were completely blocked by inhibitors of phosphatidylinositol (PI)-kinase/Akt, nuclear factor (NF)-kappaB and p38 mitogen-activated protein kinase (MAPK). In accordance with the expression of IL-23p19, the phosphorylation of IkappaB, Akt and p38 MAPK in synovial fibroblasts also increased after IL-17 stimulation.
  
  
  CONCLUSIONS
  IL-23p19 is over-expressed in RA synovial fibroblasts and IL-17 appears to up-regulate the expression of IL-23p19 in RA synovial fibroblasts via PI3-kinase/Akt, NF-kappaB- and p38-MAPK-mediated pathways. These results suggest that a disruption of interaction between IL-17 and IL-23p19 may provide a new therapeutic approach in the treatment of RA.
authors.affiliation: Department of Internal Medicine, School of Medicine, Konkuk University, Seoul, Korea.
authors.forename: H-R
authors.initials: HR
authors.lastname: Kim
authors.forename: M-L
authors.initials: ML
authors.lastname: Cho
authors.forename: K-W
authors.initials: KW
authors.lastname: Kim
authors.forename: J-Y
authors.initials: JY
authors.lastname: Juhn
authors.forename: S-Y
authors.initials: SY
authors.lastname: Hwang
authors.forename: C-H
authors.initials: CH
authors.lastname: Yoon
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.forename: S-H
authors.initials: SH
authors.lastname: Lee
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: H-Y
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases