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タイトル: | Pluripotent Stem Cell Model of Nakajo-Nishimura Syndrome Untangles Proinflammatory Pathways Mediated by Oxidative Stress |
著者: | Honda-Ozaki, Fumiko Terashima, Madoka Niwa, Akira Saiki, Norikazu Kawasaki, Yuri Ito, Haruna Hotta, Akitsu https://orcid.org/0000-0002-2619-7441 (unconfirmed) Nagahashi, Ayako Igura, Koichi Asaka, Isao Li, Hongmei Lisa Yanagimachi, Masakatsu Furukawa, Fukumi Kanazawa, Nobuo Nakahata, Tatsutoshi Saito, Megumu K. |
著者名の別形: | 尾﨑(本田), 富美子 寺嶋, 聖佳 丹羽, 明 佐伯, 憲和 川崎, ゆり 堀田, 秋津 浅香, 勲 中畑, 龍俊 斎藤, 潤 |
キーワード: | Nakajo-Nishimura syndrome (NNS) proteasome subunit beta type 8 (PSMB8) disease-specific induced pluripotent stem cells reactive oxygen species (ROS) myeloid cells |
発行日: | 5-Jun-2018 |
出版者: | Elsevier BV |
誌名: | Stem cell reports |
巻: | 10 |
号: | 6 |
開始ページ: | 1835 |
終了ページ: | 1850 |
抄録: | Nakajo-Nishimura syndrome (NNS) is an immunoproteasome-associated autoinflammatory disorder caused by a mutation of the PSMB8 gene. Although dysfunction of the immunoproteasome causes various cellular stresses attributed to the overproduction of inflammatory cytokines and chemokines in NNS, the underlying mechanisms of the autoinflammation are still largely unknown. To investigate and understand the mechanisms and signal pathways in NNS, we established a panel of isogenic pluripotent stem cell (PSC) lines with PSMB8 mutation. Activity of the immunoproteasome in PSMB8-mutant PSC-derived myeloid cell lines (MT-MLs) was reduced even without stimulation compared with non-mutant-MLs. In addition, MT-MLs showed an overproduction of inflammatory cytokines and chemokines, with elevated reactive oxygen species (ROS) and phosphorylated p38 MAPK levels. Treatment with p38 MAPK inhibitor and antioxidants decreased the abnormal production of cytokines and chemokines. The current PSC model revealed a specific ROS-mediated inflammatory pathway, providing a platform for the discovery of alternative therapeutic options for NNS and related immunoproteasome disorders. |
著作権等: | © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
URI: | http://hdl.handle.net/2433/233014 |
DOI(出版社版): | 10.1016/j.stemcr.2018.04.004 |
PubMed ID: | 29731430 |
出現コレクション: | 学術雑誌掲載論文等 |
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