Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by IL-17 through PI3-kinase-, NF-kappa B- and p38 MAPK-dependent signalling pathways

作者：Kim H R; Cho M L; Kim K W; Juhn J Y; Hwang S Y; Yoon C H; Park S H; Lee S H; Kim H Y^*

来源：Rheumatology, 2007, 46(1): 57-64.

DOI：10.1093/rheumatology/kel159

• rheumatoid arthritis
• synovial fibroblast
• IL-23
• IL-17

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)-kappa B and p38 mitogen-activated protein kinase (MAPK). In accordance with the expression of IL-23p19, the phosphorylation of I kappa B, 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-kappa B- 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.

• 出版日期2007-1
• 单位河北医科大学