We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by IL-17 through PI3-kinase-, NF-κB- and p38 MAPK-dependent signalling pathways.
- Authors
H.-R. Kim; M.-L. Cho; K.-W. Kim; J.-Y. Juhn; S.-Y. Hwang; C.-H. Yoon; S.-H. Park; S.-H. Lee; H.-Y. Kim
- 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)-κB and p38 mitogen-activated protein kinase (MAPK). In accordance with the expression of IL-23p19, the phosphorylation of IκB, Akt and p38 MAPK in synovial fibroblasts also increased after IL-17 stimulation.Conclusion. 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-κB- 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.
- Subjects
INTERLEUKINS; RHEUMATOID arthritis; FIBROBLASTS; SERUM
- Publication
Rheumatology, 2007, Vol 46, Issue 1, p57
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/kel159