{"created":"2023-07-27T06:51:25.155958+00:00","id":44837,"links":{},"metadata":{"_buckets":{"deposit":"1a3688b7-b9b6-4135-bc88-31396cf84e70"},"_deposit":{"created_by":18,"id":"44837","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44837"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044837","sets":["2812:2813:2830"]},"author_link":["2881","20436"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2004-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"6p.","bibliographicVolumeNumber":"2002-2003","bibliographic_titles":[{"bibliographic_title":"平成15(2003)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2003 Fiscal Year Final Research Report","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":"重症感染症やショック症候群など、強い生体反応を伴う急性炎症性疾患では単球活性化に伴うサイトカイン産生がショック症状や全身臓器傷害など、いわゆるマクロファージ活性化症候群と呼ばれる病態を惹起することが知られている。病原体の侵入に伴うこのような致死的な生体反応を防ぐためには、過剰な炎症反応を制御し、感染の終息に向かう免疫応答が正常に機能することが必要とされる。また種々の炎症性疾患では、組織や臓器にマクロファージが浸潤、これが病態形成に積極的に関与していることが想定されているが、一方でマクロファージ自身が炎症を制御する役割を果たしている可能性も示唆される。このような単球・マクロファージ由来の炎症制御因子として注目されるのが、ヘムオキシゲナーゼ1(HO-1)ならびにその代謝産物である。\nHO-1の産生は種々のストレス刺激により速やかに誘導されること、我々が報告したHO-1欠損症では恒常的に強い炎症反応が観察されたことなどから、本酵素が単球を中心とした免疫応答の調節機構として決定的な働きをしている可能性が示唆される。またHO-1遺伝子上流のpromotor領域にあるGTくり返し配列の多型がHO-1発現レベルと関連し種々の炎症性疾患の発症に関与している可能性が報告されている。このことは、HO-1欠損例でなくても、HO-1遺伝子あるいはpromotor領域の遺伝子多型によりHO-1発現の量的な変化が起こり、炎症病変の増悪に関与する可能性を示唆している。\n本研究では末梢血単核球によるHO-1産生調節機構を解明し種々の炎症疾患の病態形成におけるHO-1産生細胞の関与を明らかにすること、さらにHO-1を利用した新たな炎症制御戦略の開発を目的として、種々の検討を行った。\n今回の検討では、末梢血白血球の内、単球がHO-1産生の主体であること、種々の急性炎症性疾患では単球のHO-1産生が亢進することが示された。また、このような単球によるHO-1産生の亢進が種々の単球表面抗原発現の変化を伴う、単球活性化により誘導されることが示唆された。さらに、HO-1産生が単球の一部の分画に選択的に認められることから、これらの単球亜群を標的として、抗炎症剤による治療戦略の開発をすすめることが可能であると考えられた。","subitem_description_type":"Abstract"},{"subitem_description":"Savere infection and shock syndromes are often associated with intense body reactions called macrophage activation syndrome, characteried by monocyte activation, hypercytokinemia, circulatory failure and multiple organ dysfunction.To prevent these deleterious consequenoes upon pathogen exposure, the body defense system has to be supplied not only with effective antigen-specific immune response, but at the same time with tightly controlled regulatory system of inflammation.Previous reports indicated that macrophages infiltrate into various organs in various inflammatory illnesses and they contribute to the pathogenesis of organ injury.But at the same time, it is suggested that mecrophages themselves play roles in counteracting inflammation locally.Heme oxygenase-1(HO-1) and its related products are the groups of key molecules produced by monocytes/macrophages to regulate excessive inflammatory reactions.\nWe have previously shown that HO-1 production is rapidly induced in circulating mono cytes upon oxidative stress and a patient with HO-1 deficiency was associated with sustained inflammation throughout his life.These findings suggesed that monocytes play cardinal roles in controlling the level of inflammation during various inflammatory illnesses in vivo. In addition, GT repeat polymorphism within the promoter region of HO-1 gene is associated with the levels of induced HO-1 activity.Furthermore, epidemiological studies have shown that there exist strong correlation between the length of GT repeats and the incidence of multiple of inflammatory illnesses.These studies indicate that the levels of inducible HO-1 controls the intensity of inflammatory reaction elicited upon certain oxidative stresses.\nIn this study regulatory mechanism of HO-1 production by circulating monocytes was analyzed and tried to darify the role of HO-1 in the pathogenesis of various inflammatory disorders.Based on these findings, further studies were performed to develop a novel therapeutic approach to counteract excessive inflammation, by modulating HO-1 production in vivo.\nIt was shown in this study that circulating monocytes are the major producer of HO-1 both in vivo andin vitro.HO-1 production by activated monocytes was associated with phenotypical changes in monocytes during acute inflammation.HO-1 production was preferentially observed within a particular subpopulation of monocytes, indicating that it is possible to direct the development of anti-inflammatory therapy by manipulating the numbers and functions of This particular subpopulation of monocytes.","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:14570729, 研究期間(年度):2002-2003","subitem_description_type":"Other"},{"subitem_description":"出典：「ヘムオキシゲナーゼ1による炎症制御機構の解析と新しい炎症治療戦略に関する研究」研究成果報告書　課題番号14570729\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　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00051176","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医薬保健研究域医学系"}]},"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=40210281"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=40210281","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14570729/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14570729/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14570729/145707292003kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14570729/145707292003kenkyu_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":"2018-06-22"}],"displaytype":"detail","filename":"HO-PR-YACHIE-A-kaken 2004-6p.pdf","filesize":[{"value":"317.5 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"HO-PR-YACHIE-A-kaken 2004-6p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44837/files/HO-PR-YACHIE-A-kaken 2004-6p.pdf"},"version_id":"4fb7c30e-c3e7-4cb6-9a0f-4bf82bba2c20"}]},"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":"ヘムオキシゲナーゼ1による炎症制御機構の解析と新しい炎症治療戦略に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"ヘムオキシゲナーゼ1による炎症制御機構の解析と新しい炎症治療戦略に関する研究"},{"subitem_title":"Research on regulatory mechanism of inflammation by HO-1 and development of novel anti-inflammatory threrapy","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2830"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-06-22"},"publish_date":"2018-06-22","publish_status":"0","recid":"44837","relation_version_is_last":true,"title":["ヘムオキシゲナーゼ1による炎症制御機構の解析と新しい炎症治療戦略に関する研究"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:35:46.959963+00:00"}