title: A significant induction of neutrophilic chemoattractants but not RANKL in synoviocytes stimulated with interleukin 17.
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.
authors.affiliation: Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, Iruma-gun, Saitama, 350-0495, Japan.
authors.forename: Muneo
authors.initials: M
authors.lastname: Ota
authors.forename: Maiko
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tachibana
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yokota
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Araki
authors.forename: Kojiro
authors.initials: K
authors.lastname: Sato
authors.forename: Toshihide
authors.initials: T
authors.lastname: Mimura
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism; D019070:Cell Lineage; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004872:Ergocalciferols / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology*; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology; D053245:RANK Ligand / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D002630:Chemotactic Factors; D004872:Ergocalciferols; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C003564:1,25-dihydroxyergocalciferol; D015232:Dinoprostone