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Expression of interleukin-18, IL-18BP, and IL-18R in serum, synovial fluid, and synovial tissue in patients with rheumatoid arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic immunological disease, the invasive monocytes/macrophages and lymphocytes present in synovial cells and synovial tissue produce many cytokines and inflammatory mediators by paracrine signaling and plays a role in the pathological progress in RA patients. Interleukin-18 (IL-18) is a representative proinflammatory factor and displays multiple biological functions. This study was designed to investigate the expression of IL-18 and its receptor (IL-18R) and IL-18 binding protein (IL-18BP) in serum, synovial fluid, and synovial tissue of patients with RA, and to identify the pathological role of IL-18 in RA. Serum, synovial fluid, and synovial tissue were obtained from RA patients. Samples from patients with osteoarthritis and healthy people were obtained as controls. Levels of IL-18, IL-18BP, and PGE2 in serum and synovial fluid were measured by enzyme-linked immunosorbent assay. The biological activity of IL-18 in serum and synovial fluid was detected on the basis of IFN-γ secretion from IL-18-responding human myelomonocytic KG-1 cells. NO in serum and synovial fluid was detected by Griess reaction. Expression of IL-18, IL-18BP, IL-18R, iNOS, and COX-2 mRNA and protein in synovial tissues was determined by quantitative reverse transcriptase polymerase chain reaction and Western blot. This study shows the expression levels of IL-18, IL-18R, iNOS, COX-2, and the biological activity of IL-18 in both serum and synovial fluid and tissue of patients with RA were significantly increased compared with the corresponding samples from the two control groups. In addition, expression of IL-18BP in patients with RA was decreased compared with samples from the two control groups. In conclusion, the overexpression of IL-18 and IL-18R may play an important role in the pathogenesis of RA.

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Acknowledgments

This work was supported by grants from the Traditional Chinese Medicine Foundation (No. 2008CA047, No. 2004C086, No. 2006Y007), and the Medical and Health Science Foundation (No. 2004B069, No. 2006C166) of Zhejiang Province, China. This paper is proofread by a native English professional with science background at Elixigen Corporation.

Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China

    Xue-Ting Shao, Lei Feng, Ting-Ting Feng, Yun-Mei Yang, Nan-Ping Wu & Hang-Ping Yao

  2. Institute of Immunology, Zhejiang University, Hangzhou, China

    Li-Juan Gu

  3. College of Medicine, Taizhou University, Taizhou, China

    Li-Juan Wu

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  1. Xue-Ting Shao
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Correspondence to Nan-Ping Wu or Hang-Ping Yao.

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X.-T. Shao and L. Feng have contributed equally to this work.

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Shao, XT., Feng, L., Gu, LJ. et al. Expression of interleukin-18, IL-18BP, and IL-18R in serum, synovial fluid, and synovial tissue in patients with rheumatoid arthritis. Clin Exp Med 9, 215–221 (2009). https://doi.org/10.1007/s10238-009-0036-2

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  • DOI: https://doi.org/10.1007/s10238-009-0036-2

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