Journal of Bone and Mineral Metabolism

, Volume 33, Issue 1, pp 40–47

A significant induction of neutrophilic chemoattractants but not RANKL in synoviocytes stimulated with interleukin 17

Authors

  • Muneo Ota
    • Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical University
  • Maiko Yanagisawa
    • Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical University
  • Hideyuki Tachibana
    • Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical University
  • Kazuhiro Yokota
    • Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical University
  • Yasuto Araki
    • Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical University
    • Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical University
  • Toshihide Mimura
    • Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical University
Original Article

DOI: 10.1007/s00774-014-0565-y

Cite this article as:
Ota, M., Yanagisawa, M., Tachibana, H. et al. J Bone Miner Metab (2015) 33: 40. doi:10.1007/s00774-014-0565-y

Abstract

Interleukin 17 (IL-17) is a cytokine implicated in the promotion of osteoclastogenesis. Its effect has been believed not to be directly exerted on osteoclast precursors, but rather indirectly carried out via an induction of receptor activator of NF-κB ligand (RANKL), the osteoclast differentiation factor, on osteoclast-supporting cells, which in turn exert an effect on osteoclast precursors. The mechanistic details, however, remain unclear. In this study, we first performed a transcriptome analysis of synoviocytes derived from a patient with rheumatoid arthritis cultured in the presence or absence of IL-17. We discovered that most of the genes significantly induced by IL-17 were chemokines with a chemotactic effect on neutrophils. We confirmed these results by quantitative RT-PCR and ELISA. Unexpectedly, the stimulation with IL-17 alone did not induce the expression of RANKL either at the mRNA or the protein level. The induction of RANKL was observed when IL-17 was added in combination with 1,25-dihydroxyvitamin D3 and prostaglandin E2, well-known inducers of RANKL, although the exact mechanism of this synergistic effect remains unclear. IL-6 and monocyte chemoattractant protein-1 were also significantly induced by IL-17 at both the mRNA and protein levels. Thus, it appears that IL-17 induces the migration of neutrophils and monocytes/macrophages through the activation of synoviocytes, and enhances a positive feedback loop composed of proinflammatory cytokines IL-6 and IL-17.

Keywords

Interleukin 17 Osteoclast Synoviocytes Rheumatoid arthritis

Abbreviations

IL

Interleukin

RANKL

Receptor activator of NF-κB ligand

RA

Rheumatoid arthritis

ODF

Osteoclast differentiation factor

M–CSF

Macrophage colony stimulating factor

IFN

Interferon

FCS

Fetal calf serum

CXCL

Chemokine (C–X–C motif) ligand

CCL

Chemokine (C–C motif) ligand

VD3

1,25-dihydroxyvitamin D3

PGE2

Prostaglandin E2

TRAP

Tartrate-resistant acid phosphatase

MCP-1

Monocyte chemoattractant protein-1

Supplementary material

774_2014_565_MOESM1_ESM.pdf (27 kb)
Supplementary material 1 (PDF 27 kb)

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2014