Jun-Ichiro Kan1, Shintaro Mishima1, Jun-Ichi Kashiwakura2, Tomomi Sasaki-Sakamoto3, Masayuki Seki4, Shu Saito4, Chisei Ra5, Yasuaki Tokuhashi4, Yoshimichi Okayama6. 1. Allergy and Immunology Project Team, Nihon University School of Medicine, Tokyo, Japan; Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan. 2. Allergy and Immunology Project Team, Nihon University School of Medicine, Tokyo, Japan; Laboratory for Allergic Disease, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan; Division of Medical Education Planning and Development, Nihon University School of Medicine, Tokyo, Japan. 3. Allergy and Immunology Project Team, Nihon University School of Medicine, Tokyo, Japan; Division of Medical Education Planning and Development, Nihon University School of Medicine, Tokyo, Japan. 4. Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan. 5. Department of Microbiology, Nihon University School of Medicine, Tokyo, Japan. 6. Allergy and Immunology Project Team, Nihon University School of Medicine, Tokyo, Japan; Division of Medical Education Planning and Development, Nihon University School of Medicine, Tokyo, Japan. Electronic address: okayama.yoshimichi@nihon-u.ac.jp.
Abstract
BACKGROUND: Interleukin (IL)-17A plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). The expression of IL-17A in synovial mast cells (MCs) in RA and osteoarthritis (OA) has been reported, but the frequencies of IL-17A expression in synovial MCs have varied. The aim of this study was to investigate whether IL-17A expression is upregulated in human synovial MCs in RA and to elucidate the mechanism of IL-17A expression in synovial MCs. METHODS: Synovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Synovium-derived cultured MCs were generated by culturing synovial cells with stem cell factor. IL-17A expression was investigated using immunofluorescence in synovial tissues. IL-17A mRNA expression and its production from MCs were examined using RT-PCR and ELISA, respectively. RESULTS: The number of IL-17A-positive ((+)) synovial MCs and the percentage of IL-17A(+) MCs among all the IL-17A(+) cells from RA patients were not significantly increased compared with those from OA subjects. The synovium-derived cultured MCs spontaneously released small amounts of IL-17A. Neither IgE- nor IgG-dependent stimulation increased IL-17A production from the MCs. IL-33, tumor necrosis factor-α, C5a, lipopolysaccharide or IL-23 plus IL-1β did not affect IL-17A production in MCs. CONCLUSIONS: The synovial MCs are not a main source of IL-17A in RA.
BACKGROUND: Interleukin (IL)-17A plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). The expression of IL-17A in synovial mast cells (MCs) in RA and osteoarthritis (OA) has been reported, but the frequencies of IL-17A expression in synovial MCs have varied. The aim of this study was to investigate whether IL-17A expression is upregulated in human synovial MCs in RA and to elucidate the mechanism of IL-17A expression in synovial MCs. METHODS: Synovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Synovium-derived cultured MCs were generated by culturing synovial cells with stem cell factor. IL-17A expression was investigated using immunofluorescence in synovial tissues. IL-17A mRNA expression and its production from MCs were examined using RT-PCR and ELISA, respectively. RESULTS: The number of IL-17A-positive ((+)) synovial MCs and the percentage of IL-17A(+) MCs among all the IL-17A(+) cells from RApatients were not significantly increased compared with those from OA subjects. The synovium-derived cultured MCs spontaneously released small amounts of IL-17A. Neither IgE- nor IgG-dependent stimulation increased IL-17A production from the MCs. IL-33, tumor necrosis factor-α, C5a, lipopolysaccharide or IL-23 plus IL-1β did not affect IL-17A production in MCs. CONCLUSIONS: The synovial MCs are not a main source of IL-17A in RA.
Authors: Nataliya V Mushenkova; Nikita G Nikiforov; Nikolay K Shakhpazyan; Varvara A Orekhova; Nikolay K Sadykhov; Alexander N Orekhov Journal: Int J Mol Sci Date: 2022-07-29 Impact factor: 6.208