caa a22 4500 60546359X CHVBK 20210128100254.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s00774-014-0575-9 doi (NATIONALLICENCE)springer-10.1007/s00774-014-0575-9 Mycobacterium tuberculosis promotes arthritis development through toll-like receptor 2 [Elektronische Daten] [Hiroya Kanagawa, Yasuo Niki, Tami Kobayashi, Yuiko Sato, Eri Katsuyama, Atsuhiro Fujie, Wu Hao, Kana Miyamoto, Toshimi Tando, Ryuichi Watanabe, Mayu Morita, Hideo Morioka, Morio Matsumoto, Yoshiaki Toyama, Takeshi Miyamoto] Rheumatoid arthritis (RA) is a multifactorial disease caused by genetic and environmental factors: however, precise molecular mechanisms underlying its pathogenesis remain largely unknown. Treatment of RA patients with disease-modifying biological agents occasionally promotes Mycobacterium tuberculosis infection or recurrence of M. tuberculosis, although how infection promotes arthritis has not been characterized. Here, we found that arthritis phenotypes in a collagen-induced mouse model were evident only when killed M. tuberculosis was co-administered. Treatment of cultured macrophages with killed M. tuberculosis promoted production of IL-6, a major inflammatory cytokine in RA patients, while similar treatment of TLR2-deficient macrophages failed to induce IL-6 expression. Arthritis scores, joint destruction, and serum IL-6 levels were all significantly ameliorated in TLR2-deficient compared with wild-type mice, even in animals treated with killed M. tuberculosis. These results suggest that M. tuberculosis infection enhances arthritis development and that TLR2 could serve as a therapeutic target for some forms of the disease. The Japanese Society for Bone and Mineral Research and Springer Japan, 2014 Mycobacterium tuberculosis nationallicence Rheumatoid arthritis nationallicence Toll-like receptor 2 nationallicence IL-6 nationallicence RA : Rheumatoid arthritis nationallicence TLRs : Toll-like receptors nationallicence CIA : Collagen-induced arthritis nationallicence Kanagawa Hiroya Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Niki Yasuo Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Kobayashi Tami Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Sato Yuiko Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Katsuyama Eri Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Fujie Atsuhiro Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Hao Wu Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Miyamoto Kana Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Tando Toshimi Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Watanabe Ryuichi Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Morita Mayu Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Morioka Hideo Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Matsumoto Morio Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Toyama Yoshiaki Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Miyamoto Takeshi Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut Journal of Bone and Mineral Metabolism Springer Japan 33/2(2015-03-01), 135-141 0914-8779 33:2<135 2015 33 774 https://doi.org/10.1007/s00774-014-0575-9 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/s00774-014-0575-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kanagawa Hiroya Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Niki Yasuo Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Kobayashi Tami Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Sato Yuiko Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Katsuyama Eri Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Fujie Atsuhiro Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Hao Wu Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Miyamoto Kana Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Tando Toshimi Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Watanabe Ryuichi Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Morita Mayu Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Morioka Hideo Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Matsumoto Morio Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Toyama Yoshiaki Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 700 1- Miyamoto Takeshi Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan aut NATIONALLICENCE 773 0- Journal of Bone and Mineral Metabolism Springer Japan 33/2(2015-03-01), 135-141 0914-8779 33:2<135 2015 33 774