Increased synovial expression of IL-27 by IL-17 in rheumatoid arthritis

Inflamm Res. 2012 Dec;61(12):1339-45. doi: 10.1007/s00011-012-0534-7. Epub 2012 Jul 24.

Abstract

Objectives and design: Interleukin (IL) 17 plays an important role in synovial inflammation and bone destruction in rheumatoid arthritis (RA), while IL-27 exerts a regulatory role in T cell-mediated immune responses. Our aim was to study the influence of IL-17 on IL-27 production in RA.

Materials and methods: Following injection of IL-17 in the knee joint of CIA mice, synovium was examined for IL-17 and IL-27 expression by western blot, real-time PCR, and immunohistochemistry. IL-17 and IL-27 levels were measured by ELISA in mouse bone marrow-derived dendritic cells (BM-DCs) and in synovial fluid (SF) macrophages from RA patients.

Results: IL-17 exacerbated disease progression in CIA mice. Histological analysis showed increased pannus formation associated with cartilage and bone erosion following injection with IL-17. The expression of IL-27 was increased in CIA mice. The expression of IL-17 and IL-27 was increased more in IL-17-injected CIA mice than in control mice. The majority of cells expressing IL-27 were co-localized with synovial macrophages. Increased expression of IL-27 by application of recombinant IL-17 was confirmed in CIA BM-DCs and in SF macrophages from RA patients.

Conclusion: IL-17 enhanced expression of IL-27 in synovial macrophages from RA patients and CIA mice, indicating an interaction between IL-17 and IL-27 as an autoregulatory mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Rheumatoid / immunology*
  • Bone Marrow Cells / cytology
  • Dendritic Cells / immunology
  • Humans
  • Interleukin-17 / immunology*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Knee Joint
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred DBA
  • RNA, Messenger / metabolism
  • Synovial Membrane / immunology*

Substances

  • Il27 protein, mouse
  • Interleukin-17
  • Interleukins
  • MYDGF protein, human
  • RNA, Messenger