{"created":"2023-06-19T09:10:02.954421+00:00","id":21509,"links":{},"metadata":{"_buckets":{"deposit":"f72ff5bf-a778-49c1-a616-fb898208b956"},"_deposit":{"created_by":1,"id":"21509","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"21509"},"status":"published"},"_oai":{"id":"oai:kumadai.repo.nii.ac.jp:00021509","sets":["343:347:348:349"]},"author_link":["92396"],"item_14_alternative_title_22":{"attribute_name":"その他の言語のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Rolo of T cells in APAP-induced hepatotoxicity and its modulation by overexpression of SOCS3 in T cells"}]},"item_14_alternative_title_23":{"attribute_name":"タイトル（ヨミ）","attribute_value_mlt":[{"subitem_alternative_title":"アセトアミノフェン カンショウガイ ジ ニ オケル Tサイボウ ノ ヤクワリ ト SOCS3 カジョウ ハツゲン ニ ヨル シュウショク"}]},"item_14_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2006-03-24","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{}]}]},"item_14_creator_3":{"attribute_name":"別言語の著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"沼田, 亨祐","creatorNameLang":"ja"},{"creatorName":"ヌマタ, コウスケ","creatorNameLang":"ja-Kana"},{"creatorName":"Numata, Kosuke","creatorNameLang":"en"}],"familyNames":[{"familyName":"沼田","familyNameLang":"ja"},{"familyName":"ヌマタ","familyNameLang":"ja-Kana"},{"familyName":"Numata","familyNameLang":"en"}],"givenNames":[{"givenName":"亨祐","givenNameLang":"ja"},{"givenName":"コウスケ","givenNameLang":"ja-Kana"},{"givenName":"Kosuke","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"92396","nameIdentifierScheme":"WEKO"}]}]},"item_14_description_17":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"},{"subitem_description":"application/pdf","subitem_description_type":"Other"},{"subitem_description":"text/plain","subitem_description_type":"Other"}]},"item_14_description_46":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"学位論文(Thesis)","subitem_description_type":"Other"}]},"item_14_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"サイトカインはアセトアミノフェン肝傷害の進行に関与している。SOCS蛋白はJAK/STAT経路を阻害することによりサイトカインのシグナル伝達を調整しているが、SOCS蛋白のアセトアミノフェンによる肝毒性に対する役割は知られていない。今回の研究は、アセトアミノフェンによる肝傷害に対するT細胞内SOCS3の役割を説明した。T細胞特異的にSOCS3を過剰発現させたマウス(SOCS3Tg)は、野生型マウスと比較しALT値の上昇、肝細胞壊死の増強、生存率の減少によりアセトアミノフェン投与後の肝傷害を悪化させた。野生型マウスまたはT細胞、B細胞の欠損したRAG2-/-マウスにSOCS3Tg-CD4+T細胞を移入しても同じ結果が再現された。SOCS3Tgマウスでは肝細胞アポトーシスは肝細胞内の抗アポトーシス蛋白であるbcl-2の減少により、また肝細胞再生能は細胞周期調節蛋白の変化により減弱した。血液中のIFNγとTNFαはコントロールと比較するとSOCS3Tgマウスにて増強していた。中和抗体による実験にてSOCS3Tgマウスでは、上昇したIFNγとTNFαが肝毒性を増強させていた。肝傷害において有害であるSTAT1の活性化はSOCS3Tgマウスで増加していた。一方、肝細胞保護に働くSTAT3活性はSOCS3Tgマウスにて減少しており、これは肝細胞内のSOCS3の発現の減少によるものと思われた。以上の結果より、T細胞内のSOCS3の過剰発現はおそらくIFNγとTNFαの上昇を介した肝細胞内のSTAT1の上昇、STAT3の減少によりアセトアミノフェンによる肝毒性が増強したものと考えられた。","subitem_description_type":"Other"}]},"item_14_publisher_36":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"熊本大学"}]},"item_14_subject_20":{"attribute_name":"日本十進分類法","attribute_value_mlt":[{"subitem_subject":"377.5","subitem_subject_scheme":"NDC"}]},"item_14_text_18":{"attribute_name":"形態","attribute_value_mlt":[{"subitem_text_value":"3895628 bytes"},{"subitem_text_value":"60931 bytes"},{"subitem_text_value":"65532 bytes"}]},"item_14_text_47":{"attribute_name":"資源タイプ・ローカル","attribute_value_mlt":[{"subitem_text_value":"博士論文"}]},"item_14_text_48":{"attribute_name":"資源タイプ・NII","attribute_value_mlt":[{"subitem_text_value":"Thesis or Dissertation"}]},"item_14_text_49":{"attribute_name":"資源タイプ・DCMI","attribute_value_mlt":[{"subitem_text_value":"text"}]},"item_14_text_50":{"attribute_name":"資源タイプ・ローカル表示コード","attribute_value_mlt":[{"subitem_text_value":"03"}]},"item_14_text_81":{"attribute_name":"学位番号","attribute_value_mlt":[{"subitem_text_value":"甲博医第1570号"}]},"item_14_version_type_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"沼田, 亨祐","creatorNameLang":"ja"},{"creatorName":"ヌマタ, コウスケ","creatorNameLang":"ja-Kana"},{"creatorName":"Numata, Kosuke","creatorNameLang":"en"}],"familyNames":[{"familyName":"沼田","familyNameLang":"ja"},{"familyName":"ヌマタ","familyNameLang":"ja-Kana"},{"familyName":"Numata","familyNameLang":"en"}],"givenNames":[{"givenName":"亨祐","givenNameLang":"ja"},{"givenName":"コウスケ","givenNameLang":"ja-Kana"},{"givenName":"Kosuke","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"92396","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-03-02"}],"displaytype":"detail","filename":"22-1570.pdf","filesize":[{"value":"3.9 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"22-1570.pdf","url":"https://kumadai.repo.nii.ac.jp/record/21509/files/22-1570.pdf"},"version_id":"4f10beeb-922e-4ae0-a87f-4dfa7ebaf73b"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"肝傷害","subitem_subject_scheme":"Other"},{"subitem_subject":"サイトカイン","subitem_subject_scheme":"Other"},{"subitem_subject":"T細胞","subitem_subject_scheme":"Other"},{"subitem_subject":"細胞傷害","subitem_subject_scheme":"Other"},{"subitem_subject":"アポトーシス","subitem_subject_scheme":"Other"},{"subitem_subject":"細胞増殖","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"アセトアミノフェン肝傷害時におけるT細胞の役割とSOCS3過剰発現による修飾","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"アセトアミノフェン肝傷害時におけるT細胞の役割とSOCS3過剰発現による修飾"}]},"item_type_id":"14","owner":"1","path":["349"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-08-13"},"publish_date":"2014-08-13","publish_status":"0","recid":"21509","relation_version_is_last":true,"title":["アセトアミノフェン肝傷害時におけるT細胞の役割とSOCS3過剰発現による修飾"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-09-13T05:20:18.078171+00:00"}