{"created":"2023-07-27T07:00:08.607691+00:00","id":59965,"links":{},"metadata":{"_buckets":{"deposit":"6fe1cde5-f711-4867-af35-2bdd4ced3bcb"},"_deposit":{"created_by":18,"id":"59965","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"59965"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00059965","sets":["2812:2813:2836"]},"author_link":["21546","22481"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"1999-03-15","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"1995 – 1997","bibliographic_titles":[{"bibliographic_title":"平成9(1997)年度 科学研究費補助金 基盤研究(A) 研究成果報告書概要"},{"bibliographic_title":"1997 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"我々は急性炎症反応における好中球浸潤に本質的な役割を担っているIL-8に対するマウス単クローン性抗ヒトIL-8抗体のヒト型化をCDR(complementarity determining region)graftingにより完成し、現在大量発現に成功した。この抗体の標的とする臨床疾患を特定するためにウサギを用いた様々な急性炎症モデル作製し、その効果を確認している。中でもより臨床病態に近いモデルとして敗血症誘導性ARDSモデルや脳虚血後再潅流モデルを作製した。これらのモデルにおいては、抗IL-8抗体投与により病態悪化を著明に抑制することが明らかとなり、ヒト型化抗IL-8抗体の臨床応用の可能性を示唆する結果となった。一方、NF-kBを標的とした抗炎症剤開発については、我々はヒト単球系細胞株THP-1細胞抽出液中にIKBαに会合してリン酸化するIKBa会合キナーゼを同定し、そのリン酸化部位がIKBαのC末端領域酸性ドメインのSer/Thr残基であることを見いだした。しかもその後の研究から、これはカゼインキナーゼIIやTNFα及びIL-1のシグナル伝達系における同様の機能を有するキナーゼ(IKKα,β)とは異なるIKBα会合C末端キナーゼであることがわかり、この酸素の精製をすすめ成功した。SDS-PAGEの結果、分子量約40Kdで、精製酵素は293のセリンを主にリン酸化することが明らかとなった。しかし遺伝子クローニングの目的で蛋白の微量分析を試みたが、N末端の閉鎖により結果は得られず、さらにLys-C消化物をTOF-MSにより分析したが結果は得られず、現在さらに酵素の精製をすすめ、蛋白の微量分析としてのマススペクトロメトリーを含め、検討を行っている。","subitem_description_type":"Abstract"},{"subitem_description":"IL-8 is essentially involved in neutrophil-dependent tissue damage in acute inflammatory reactions. We established the humanized mouse anti-human IL-8 by mean of complementarity determining region grafting and succeeded to purify the large amount of this antibody. For the application of this antibody on various clinical condition, we established various acute inflammatory ananimal models. Especially, we have established preclinical condition animal models such as acute respiratory distress syndrom-like lung injury and brain reperfusion injury. In these models, we showed that anti-IL-8 antibody treatment almostly prevented these injury. These results strongly suggest the possibility of clinical application of humarized anti-human IL-8 antibody against acute inflammatory dieases.\nWe have identified a kinase in cell extracts from the LPS-stimulated human monocytic cell line, THP-1, that specifically bind and phosphorylates IkBa. LPS-stimulation transiently enhanced the IkBa-bound kinase activity in THP-1 cells. Mutation analysis of IkBa and competition experiments with the synthetic peptides identified major phosphorylation site by the bound kinase as Ser and Thr residues in the C-terminal acidic domain of IkBa. Moreover, this IkBa-boundkinase is novel kinase but not Ikka, b which are related to signal pathway of TNF-a and IL-1. So that we try to purify the kinase SDS-PAGE analysis showed that the kinase. is 40 Kd. We are now analyzing the amino acid squence of the sample and trying to clone the gene.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:07557031, 研究期間(年度):1995 – 1997","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「IL8抗体のヒト型化とサイトカイン遺伝子調節因子NFkBを標的とした抗炎症剤開発」課題番号07557031\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） \n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07557031/075570311997kenkyu_seika_hokoku_gaiyo/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"東京大学 / 金沢大学医学部","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00066216","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=50222427"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=50222427","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557031/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557031/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07557031/075570311997kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07557031/075570311997kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-06-03"}],"displaytype":"detail","filename":"ME-PR-MATSUSHIMA-K-kaken 1999-3p.pdf","filesize":[{"value":"106.5 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-MATSUSHIMA-K-kaken 1999-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/59965/files/ME-PR-MATSUSHIMA-K-kaken 1999-3p.pdf"},"version_id":"a3dd75f2-74a1-4547-a736-738016dbfdbc"}]},"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":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"IL8抗体のヒト型化とサイトカイン遺伝子調節因子NFkBを標的とした抗炎症剤開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"IL8抗体のヒト型化とサイトカイン遺伝子調節因子NFkBを標的とした抗炎症剤開発"},{"subitem_title":"Humanization of mouse anti-human IL-8 antibody and development of anti-inflammatory agent against cytokine regulatory factor, NFkB","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2836"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-06-03"},"publish_date":"2022-06-03","publish_status":"0","recid":"59965","relation_version_is_last":true,"title":["IL8抗体のヒト型化とサイトカイン遺伝子調節因子NFkBを標的とした抗炎症剤開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T12:57:10.600672+00:00"}