caa a22 4500 605462933 CHVBK 20210128100250.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00774-014-0565-y doi (NATIONALLICENCE)springer-10.1007/s00774-014-0565-y A significant induction of neutrophilic chemoattractants but not RANKL in synoviocytes stimulated with interleukin 17 [Elektronische Daten] [Muneo Ota, Maiko Yanagisawa, Hideyuki Tachibana, Kazuhiro Yokota, Yasuto Araki, Kojiro Sato, Toshihide Mimura] 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. The Japanese Society for Bone and Mineral Research and Springer Japan, 2014 Interleukin 17 nationallicence Osteoclast nationallicence Synoviocytes nationallicence Rheumatoid arthritis nationallicence IL : Interleukin nationallicence RANKL : Receptor activator of NF-κB ligand nationallicence RA : Rheumatoid arthritis nationallicence ODF : Osteoclast differentiation factor nationallicence M-CSF : Macrophage colony stimulating factor nationallicence IFN : Interferon nationallicence FCS : Fetal calf serum nationallicence CXCL : Chemokine (C-X-C motif) ligand nationallicence CCL : Chemokine (C-C motif) ligand nationallicence VD3 : 1,25-dihydroxyvitamin D3 nationallicence PGE2 : Prostaglandin E2 nationallicence TRAP : Tartrate-resistant acid phosphatase nationallicence MCP-1 : Monocyte chemoattractant protein-1 nationallicence Ota Muneo Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut Yanagisawa Maiko Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut Tachibana Hideyuki Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut Yokota Kazuhiro Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut Araki Yasuto Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut Sato Kojiro Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut Mimura Toshihide Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut Journal of Bone and Mineral Metabolism Springer Japan 33/1(2015-01-01), 40-47 0914-8779 33:1<40 2015 33 774 https://doi.org/10.1007/s00774-014-0565-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00774-014-0565-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ota Muneo Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut NATIONALLICENCE 700 1- Yanagisawa Maiko Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut NATIONALLICENCE 700 1- Tachibana Hideyuki Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut NATIONALLICENCE 700 1- Yokota Kazuhiro Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut NATIONALLICENCE 700 1- Araki Yasuto Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut NATIONALLICENCE 700 1- Sato Kojiro Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut NATIONALLICENCE 700 1- Mimura Toshihide Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, 350-0495, Iruma-gun, Saitama, Japan aut NATIONALLICENCE 773 0- Journal of Bone and Mineral Metabolism Springer Japan 33/1(2015-01-01), 40-47 0914-8779 33:1<40 2015 33 774