Abstract
IntroductionThe immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts.MethodsThe transcript levels of IL-29 and its specific receptor IL-28Rα in peripheral blood mononuclear cells (PBMC) and synovium were determined by real-time reverse transcription-polymerase chain reaction (real-time PCR). The concentrations of IL-29 in serum and synovial fluid (SF) were quantified by enzyme-linked immunoassay (ELISA), and the correlation of serum IL-29 levels with disease activity in RA patients was investigated. Furthermore, the expression of IL-29 in RA synovium was examined by immunohistochemistry and double immunofluorescence analysis. Finally, the expression of IL-6, IL-8, IL-10, IL-17 and matrix metalloproteinase-3 (MMP-3) in synovial fibroblasts upon IL-29 stimulation was determined by real-time PCR.ResultsIL-29 and IL-28Rα mRNA expression in PBMC was significantly increased in patients with RA compared with healthy controls (HC). The serum levels of circulating IL-29 were higher in RA than those in HC. Increased IL-29 levels were detected in RA SF when compared with osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with RA disease activity. IL-29 was mostly expressed in the lining region of RA synovium. Moreover, IL-29 was expressed predominately in synovial macrophages and fibroblasts. RA synovial fibroblasts exposed to IL-29 specifically upregulated IL-6, -8 and MMP-3 but downregulated IL-10.ConclusionsThe findings in the present study indicate, for the first time, that IL-29 is dysregulated in patients with RA, which may contribute to the RA pathogenesis via inducing the production of proinflammatory cytokines, chemokines or matrix metalloproteinases in synovial fibroblasts.
Highlights
The immunoregulatory function of interleukin (IL)-29 has recently been recognized
Upregulated expression of IL-29 and its receptor transcripts in peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis (RA) patients To explore whether IL-29 was involved in the pathogenesis of RA, we first examined the expression of IL-29 mRNA and its receptor IL-28Ra in PBMC by real-time PCR
It was found that expression of IL-29 and IL-28Ra mRNA was significantly higher in RA PBMCs when compared to healthy controls (HC) (P = 0.001 and 0.0442, respectively; Figure 1A, B)
Summary
Little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts. The pathogenesis of RA remains unclear, the accumulated evidence has suggested that cytokines play an important role in the development and maintenance of RA disease activity. Considering about 30% of RA patients could experience an inadequate response to current biologics, it is still a challenge to identify key cytokines involved in RA. The upregulation of interferon-inducible genes has been found in the synovial lining regions and whole blood of patients with RA, suggesting that interferons (IFNs) may play an important role in the pathogenesis of RA [2,3]
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