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Abstract Number: 1802

Interleukin-29 Modulates Proinflammatory Cytokine Production in Synovial Inflammation of Rheumatoid Arthritis

Miaojia Zhang, Fang Wang, Lingxiao Xu and Wenfeng Tan, Department of Rheumatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, CHINA., Nanjing, China

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: interleukins (IL) and rheumatoid arthritis (RA)

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Session Information

Title: Cytokines, Mediators, and Gene Regulation

Session Type: Abstract Submissions (ACR)

Background/Purpose: The 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). We here investigated the potential role of IL-29 in the synovial inflammation of RA.

Methods: The 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.

Results: IL-29 and IL-28Rα mRNA expression in PBMC were 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. RA SF also conferred the increased IL-29 levels compared to osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with the RA disease activity. IL-29 was markedly elevated in RA synovium compared to tissues from HC, and was mostly expressed in the lining region of 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, downregualted IL-10, but showed no effect on IL-17.

Conclusion: The 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.


Disclosure:

M. Zhang,

the National Natural Science Foundation of China (No. 30901332, 81172845),

2;

F. Wang,

the National Natural Science Foundation of China (No. 30901332, 81172845),

2;

L. Xu,

the National Natural Science Foundation of China (No. 30901332, 81172845),

2;

W. Tan,

the National Natural Science Foundation of China (No. 30901332, 81172845),

2.

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