{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363388843514725504.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.4049/jimmunol.175.5.2900"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/jimmunol/article-pdf/175/5/2900/62622412/2900.pdf"}}],"dc:title":[{"@value":"Alternative Mechanism by which IFN-γ Enhances Tumor Recognition: Active Release of Heat Shock Protein 72"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n               <jats:p>IFN-γ exhibits differential effects depending on the target and can induce cellular activation and enhance survival or mediate cell death via activation of apoptotic pathways. In this study, we demonstrate an alternative mechanism by which IFN-γ enhances tumor recognition, mediated by the active release of Hsp72. We demonstrate that stimulation of 4T1 breast adenocarcinoma cells and K562 erythroleukemic cells with IFN-γ triggers the cellular stress response, which results in the enhanced expression of total Hsp72 expression without a significant increase in cell death. Intracellular expression of Hsp72 was abrogated in cells stably transfected with a mutant hsf-1 gene. IFN-γ-induced Hsp72 expression correlated with enhanced surface expression and consequent release of Hsp72 into the culture medium. Pretreatment of tumors with compounds known to the block the classical protein transport pathway, including monensin, brefeldin A, tunicamycin, and thapsigargin, did not significantly block Hsp72 release. However, pretreatment with intracellular calcium chelator BAPTA-AM or disruption of lipid rafts using methyl β-cyclodextrin completely abrogated IFN-γ-induced Hsp72 release. Biochemical characterization revealed that Hsp72 is released within exosomes and has the ability to up-regulate CD83 expression and stimulate IL-12 release by naive dendritic cells. Pretreatment with neutralizing mAb or depletion of Hsp72 completely abrogated its chaperokine function. Taken together, these findings are indicative of an additional previously unknown mechanism by which IFN-γ promotes tumor surveillance and furthers our understanding of the central role of extracellular Hsp72 as an endogenous adjuvant and danger signal.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380866924868122752","@type":"Researcher","foaf:name":[{"@value":"Maria A Bausero"}],"jpcoar:affiliationName":[{"@value":"Center for Molecular Stress Response, Boston University Medical Center and Boston University School of Medicine , Boston, MA 02118"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388843514725504","@type":"Researcher","foaf:name":[{"@value":"Robert Gastpar"}],"jpcoar:affiliationName":[{"@value":"University Hospital Regensburg, Department of Hematology and Internistic Oncology , Regensburg ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388843514725505","@type":"Researcher","foaf:name":[{"@value":"Gabriele Multhoff"}],"jpcoar:affiliationName":[{"@value":"University Hospital Regensburg, Department of Hematology and Internistic Oncology , Regensburg ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388843514725507","@type":"Researcher","foaf:name":[{"@value":"Alexzander Asea"}],"jpcoar:affiliationName":[{"@value":"Center for Molecular Stress Response, Boston University Medical Center and Boston University School of Medicine , Boston, MA 02118"},{"@value":"Division of Investigative Pathology, Department of Pathology, Scott & White Clinic and Texas A&M University System Health Science Center College of Medicine , Temple, TX 76508"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00221767"},{"@type":"EISSN","@value":"15506606"}],"prism:publicationName":[{"@value":"The Journal of Immunology"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2005-09-01","prism:volume":"175","prism:number":"5","prism:startingPage":"2900","prism:endingPage":"2912"},"reviewed":"false","dc:rights":["https://academic.oup.com/pages/standard-publication-reuse-rights"],"url":[{"@id":"https://academic.oup.com/jimmunol/article-pdf/175/5/2900/62622412/2900.pdf"}],"createdAt":"2014-04-24","modifiedAt":"2025-03-30","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004232003371648","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Stimulation of gastric ulcer healing by heat shock protein 70"}]},{"@id":"https://cir.nii.ac.jp/crid/1360017282468284160","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The Pro-Tumorigenic Role of Chemotherapy-Induced Extracellular HSP70 from Breast Cancer Cells via Intratumoral Macrophages"}]},{"@id":"https://cir.nii.ac.jp/crid/1360283695108079872","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Heat-Shock Proteins as Endogenous Ligands Building a Bridge Between Innate and Adaptive Immunity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285707425650432","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Hsp70 interactions with membrane lipids regulate cellular functions in health and disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285714413353984","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Spatiotemporal Regulation of Hsp90–Ligand Complex Leads to Immune Activation"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679251908096","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"A novel feature of the HSP70 family"},{"@language":"ja","@value":"HSP70 ファミリーの新たな機能"},{"@value":"キーワード解説 HSP70ファミリーの新たな機能"},{"@language":"ja-Kana","@value":"キーワード カイセツ HSP70 ファミリー ノ アラタ ナ キノウ"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.4049/jimmunol.175.5.2900"},{"@type":"CROSSREF","@value":"10.1254/fpj.143.310_references_DOI_MTq3XahejlY8nucJkDxePDTLz0D"},{"@type":"CROSSREF","@value":"10.3390/cancers15061903_references_DOI_MTq3XahejlY8nucJkDxePDTLz0D"},{"@type":"CROSSREF","@value":"10.2217/imt.12.75_references_DOI_MTq3XahejlY8nucJkDxePDTLz0D"},{"@type":"CROSSREF","@value":"10.3389/fimmu.2016.00201_references_DOI_MTq3XahejlY8nucJkDxePDTLz0D"},{"@type":"CROSSREF","@value":"10.1016/j.plipres.2019.01.004_references_DOI_MTq3XahejlY8nucJkDxePDTLz0D"},{"@type":"CROSSREF","@value":"10.1016/j.bcp.2011.06.030_references_DOI_MTq3XahejlY8nucJkDxePDTLz0D"}]}