Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis

Yu Hsiang Hsu, Hsing Hui Li, Mei Yi Hsieh, Ming Fei Liu, Kuo Yuan Huang, Lin Show Chin, Pei Chih Chen, He Hsiung Cheng, Ming Shi Chang

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106 Citations (Scopus)

Abstract

Objective. The pathogenesis of rheumatoid arthritis (RA) reflects an ongoing imbalance between proinflammatory and antiinflammatory cytokines. Interleukin-20 (IL-20) has proinflammatory properties for keratinocytes. In this study, we sought to determine whether IL-20 is involved in RA. Methods. We analyzed IL-20 levels in synovial fluid from RA patients. IL-20 and its receptors were detected in RA synovial fibroblasts (RASFs), using immunohistochemical staining. The effect of IL-20 on endoilielial cells, neutrophils, and RASFs was investigated using MTT and migration assays. The expression of IL-20 and its receptors in healthy rats and in rats with collagen-induced arthritis (CIA) was also analyzed. Soluble IL-20 receptor type I (sIL-20RI) or sIL-20RII was administered to rats with CIA by intramuscular electroporation, and the severity of arthritis was monitored. Results. RA patients expressed significantly higher levels of synovial fluid IL-20 than did the rheumatic disease controls. IL-20 and its receptors were expressed in the synovial membranes and RASFs. IL-20 induced RASFs to secrete monocyte chemoattractant protein 1, IL-6, and IL-8, and it promoted neutrophil chemotaxis, RASF migration, and endothelial cell proliferation. Both IL-20 and IL-20RI were up-reguiated in the rat CIA model. In vivo, electroporated sIL-20RI plasmid DNA decreased the severity of arthritis in the rats with CIA. Conclusion. IL-20 was up-regulated in the synovial fluid of RA patients and acted as a chemokine that attracted the migration of neutrophils and RASFs in vitro. The rat CIA model demonstrated that IL-20 was involved in the pathogenesis of arthritis, because sIL-20RI significantly reduced arthritis in rats with CIA. Thus, IL-20 may modulate the incidence and severity of arthritis and play important roles at local sites of inflammation.

Original languageEnglish
Pages (from-to)2722-2733
Number of pages12
JournalArthritis and Rheumatism
Volume54
Issue number9
DOIs
Publication statusPublished - 2006 Sep 1

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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