Rheumatology Advance Access originally published online on April 8, 2008
Rheumatology 2008 47(6):815-820; doi:10.1093/rheumatology/ken061
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Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Correspondence to: T. Kuroiwa, Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, Japan. E-mail: tkuroiwa{at}med.gunma-u.ac.jp
| Abstract |
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Objective. IL-19 is a novel cytokine of the IL-10 family. In this study, we sought to examine whether IL-19 plays a role in the pathogenesis of RA.
Methods. Expression of IL-19, IL-20 receptor 1 (IL-20R1) and IL-20R2 was examined by RT-PCR and immunohistochemical analysis in rheumatoid synovium. The effects of IL-19 on synovial cells established from rheumatoid synovium (RASCs), with regard to IL-6 production and signal transducers and activators of transcription3 (STAT3) activation, were examined by ELISA and western blot analysis, respectively. The effect of IL-19 on RASC apoptosis was examined by Hoechst staining, flow cytometry analysis of annexin V binding and caspase-3 activity.
Results. IL-19, IL-20R1 and IL-20R2 mRNA were detected by RT-PCR in synovial tissues from RA patients. Immunohistochemical analysis showed IL-19 was predominantly expressed in the hyperplastic lining layers of RA synovial tissues. The majority of IL-19-positive cells were vimentin-positive and CD68-positive synovial cells, serving as markers of fibroblasts and macrophages, respectively. IL-20R1 and IL-20R2 (IL-20Rs) were expressed in both the lining and sublining layers of RA synovium. In RASC, IL-19 was induced by lipopolysaccharide stimulation and constitutive expression of IL-20Rs was observed, suggesting IL-19 has an autocrine action. In terms of this function, IL-19 induced STAT3 activation and increased IL-6 production by RASC above the medium control. Moreover, IL-19 significantly reduced RASC apoptosis induced by serum starvation.
Conclusions. These data suggest that IL-19, produced by synovial cells, promotes joint inflammation in RA by inducing IL-6 production and decreasing synovial cell apoptosis.
KEY WORDS: Rheumatoid arthritis, Interleukin-10 family, Interleukin-19, Synovial hyperplasia, CD68, Vimentin, Synovial cells, STAT3, Interleukin-6, anti-apoptosis
Submitted 4 September 2007;
revised version accepted 28 January 2008.
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