{"created":"2023-06-20T15:49:10.418379+00:00","id":3741,"links":{},"metadata":{"_buckets":{"deposit":"da0f0d3d-1d59-4d72-afc6-31b398b41fcc"},"_deposit":{"created_by":4,"id":"3741","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3741"},"status":"published"},"_oai":{"id":"oai:hama-med.repo.nii.ac.jp:00003741","sets":["2:15:17"]},"author_link":["11034"],"item_5_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"A型インフルエンザウイルスは、気道上皮のTLR3を介して線毛活性と粘液線毛クリアランスを増強する","subitem_alternative_title_language":"ja"}]},"item_5_biblio_info_5":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-10-27","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"282","bibliographicVolumeNumber":"21","bibliographic_titles":[{"bibliographic_title":"Respiratory Research","bibliographic_titleLang":"en"}]}]},"item_5_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2021-03-16"}]},"item_5_degree_grantor_15":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"浜松医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13802","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_12":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_5_description_13":{"attribute_name":"学位の区分","attribute_value_mlt":[{"subitem_description":"doctoral","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_description_14":{"attribute_name":"学位の分野","attribute_value_mlt":[{"subitem_description":"医学系研究科","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_9":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Viral respiratory tract infections, such as influenza A virus (IAV), are common and life-threatening illnesses worldwide. The mechanisms by which viruses are removed from the respiratory tract are indispensable for airway host defense. Mucociliary clearance is an airway defense mechanism that removes pathogens from the respiratory tract. The coordination and modulation of the ciliary beating of airway epithelial cells play key roles in maintaining effective mucociliary clearance. However, the impact of respiratory virus infection on ciliary activity and mucociliary clearance remains unclear.\nMethods: Tracheal samples were taken from wild-type (WT) and Toll-like receptor 3 (TLR3)-knockout (KO) mice. Transient organ culture of murine trachea was performed in the presence or absence of IAV, polyI:C, a synthetic TLR3 ligand, and/or reagents. Subsequently, cilia-driven flow and ciliary motility were analyzed. To evaluate cilia-driven flow, red fluorescent beads were loaded into culture media and movements of the beads onto the tracheal surface were observed using a fluorescence microscope. To evaluate ciliary motility, cilia tips were labeled with Indian ink diluted with culture medium. The motility of ink-labeled cilia tips was recorded by high-speed cameras.\nResults: Short-term IAV infection significantly increased cilia-driven flow and ciliary beat frequency (CBF) compared with the control level in WT culture. Whereas IAV infection did not elicit any increases of cilia-driven flow and CBF in TLR3-KO culture, indicating that TLR3 was essential to elicit an increase of cilia-driven flow and CBF in response to IAV infection. TLR3 activation by polyI:C readily induced adenosine triphosphate (ATP) release from the trachea and increases of cilia-driven flow and CBF in WT culture, but not in TLR3-KO culture. Moreover, blockade of purinergic P2 receptors (P2Rs) signaling using P2R antagonist, suramin, suppressed polyI:C-mediated increases of cilia-driven flow and CBF, indicating that TLR3-mediated ciliary activation depended on released extracellular ATP and the autocrine ATP-P2R loop.\nConclusions: IAV infection readily increases ciliary activity and cilia-driven flow via TLR3 activation in the airway epithelium, thereby hastening mucociliary clearance and “sweeping” viruses from the airway as an initial host defense response. Mechanically, extracellular ATP release in response to TLR3 activation promotes ciliary activity through autocrine ATP-P2R loop.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_5_dissertation_number_18":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第854号"}]},"item_5_publisher_6":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Springer Nature","subitem_publisher_language":"en"}]},"item_5_relation_26":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"33109186","subitem_relation_type_select":"PMID"}}]},"item_5_relation_28":{"attribute_name":"出版社DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1186/s12931-020-01555-1","subitem_relation_type_select":"DOI"}}]},"item_5_rights_7":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.","subitem_rights_language":"en"}]},"item_5_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1465-9921","subitem_source_identifier_type":"EISSN"}]},"item_5_source_id_20":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"1465-993X","subitem_source_identifier_type":"PISSN"}]},"item_5_version_type_32":{"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_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"神谷, 陽輔","creatorNameLang":"ja"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-08-01"}],"displaytype":"detail","filename":"DT_854ronbun.pdf","filesize":[{"value":"1.5 MB"}],"format":"application/pdf","licensetype":"license_6","mimetype":"application/pdf","url":{"label":"論文本文","objectType":"fulltext","url":"https://hama-med.repo.nii.ac.jp/record/3741/files/DT_854ronbun.pdf"},"version_id":"e8ee94f2-9573-4a8d-be42-210cb91d5cae"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Influenza A virus","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"TLR3","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Ciliary activity","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Mucociliary clearance","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Airway epithelium","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium","subitem_title_language":"en"}]},"item_type_id":"5","owner":"4","path":["17"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-08-01"},"publish_date":"2021-08-01","publish_status":"0","recid":"3741","relation_version_is_last":true,"title":["Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2023-10-13T07:05:51.407272+00:00"}