Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation

Rheumatology (Oxford). 2008 Jun;47(6):815-20. doi: 10.1093/rheumatology/ken061. Epub 2008 Apr 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Humans
  • Hyperplasia / immunology
  • Interleukin-6 / biosynthesis
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Receptors, Interleukin / metabolism*
  • Recombinant Proteins / immunology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / immunology
  • Synovial Membrane / immunology*
  • Synovial Membrane / pathology


  • IL19 protein, human
  • Interleukin-6
  • Interleukins
  • Receptors, Interleukin
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • interleukin-20 receptor
  • Caspase 3