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dc.contributor.authorHonda-Ozaki, Fumiko
dc.contributor.authorTerashima, Madoka
dc.contributor.authorNiwa, Akira
dc.contributor.authorSaiki, Norikazu
dc.contributor.authorKawasaki, Yuri
dc.contributor.authorIto, Haruna
dc.contributor.authorHotta, Akitsu
dc.contributor.authorNagahashi, Ayako
dc.contributor.authorIgura, Koichi
dc.contributor.authorAsaka, Isao
dc.contributor.authorLi, Hongmei Lisa
dc.contributor.authorYanagimachi, Masakatsu
dc.contributor.authorFurukawa, Fukumi
dc.contributor.authorKanazawa, Nobuo
dc.contributor.authorNakahata, Tatsutoshi
dc.contributor.authorSaito, Megumu K.
dc.contributor.alternative尾﨑(本田), 富美子
dc.contributor.alternative寺嶋, 聖佳
dc.contributor.alternative丹羽, 明
dc.contributor.alternative佐伯, 憲和
dc.contributor.alternative川崎, ゆり
dc.contributor.alternative堀田, 秋津
dc.contributor.alternative浅香, 勲
dc.contributor.alternative中畑, 龍俊
dc.contributor.alternative斎藤, 潤
dc.date.accessioned2018-07-31T00:54:06Z-
dc.date.available2018-07-31T00:54:06Z-
dc.date.issued2018-06-05
dc.identifier.issn2213-6711
dc.identifier.urihttp://hdl.handle.net/2433/233014-
dc.description.abstractNakajo-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.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherElsevier BV
dc.rights© 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/).
dc.subjectNakajo-Nishimura syndrome (NNS)
dc.subjectproteasome subunit beta type 8 (PSMB8)
dc.subjectdisease-specific induced pluripotent stem cells
dc.subjectreactive oxygen species (ROS)
dc.subjectmyeloid cells
dc.titlePluripotent Stem Cell Model of Nakajo-Nishimura Syndrome Untangles Proinflammatory Pathways Mediated by Oxidative Stress
dc.type.niitypeJournal Article
dc.identifier.jtitleStem cell reports
dc.identifier.volume10
dc.identifier.issue6
dc.identifier.spage1835
dc.identifier.epage1850
dc.relation.doi10.1016/j.stemcr.2018.04.004
dc.textversionpublisher
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Life Science Frontiers, Center for iPS Cell Research and Application
dc.addressDepartment of Fundamental Cell Technology, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Fundamental Cell Technology, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Fundamental Cell Technology, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University・Boston Children's Hospital, Harvard Medical School
dc.addressDepartment of Pediatrics, Tokyo Medical and Dental University
dc.addressDepartment of Dermatology, Wakayama Medical University
dc.addressDepartment of Dermatology, Wakayama Medical University
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.addressDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
dc.identifier.pmid29731430
dc.identifier.kaken13389802 / 14431432 / 15549896
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