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Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma.
Higuchi, Hiroshi; Yamakawa, Natsuko; Imadome, Ken-Ichi; Yahata, Takashi; Kotaki, Ryutaro; Ogata, Jun; Kakizaki, Masatoshi; Fujita, Koji; Lu, Jun; Yokoyama, Kazuaki; Okuyama, Kazuki; Sato, Ai; Takamatsu, Masako; Kurosaki, Natsumi; Alba, Syakira Mohamad; Azhim, Azran; Horie, Ryouichi; Watanabe, Toshiki; Kitamura, Toshio; Ando, Kiyoshi; Kashiwagi, Takao; Matsui, Toshimitsu; Okamoto, Akinao; Handa, Hiroshi; Kuroda, Masahiko; Nakamura, Naoya; Kotani, Ai.
Afiliación
  • Higuchi H; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Yamakawa N; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Imadome KI; Department of Infectious Diseases, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
  • Yahata T; Research Center for Cancer Stem Cell and.
  • Kotaki R; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Ogata J; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Kakizaki M; Department of Gastroenterology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • Fujita K; Department of Molecular Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
  • Lu J; Department of Intractable Diseases, Institute of National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo, Japan.
  • Yokoyama K; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Okuyama K; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Sato A; Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • Takamatsu M; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Kurosaki N; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Alba SM; Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
  • Azhim A; Malaysia-Japan Institute of Technology, Universiti Teknologi Malaysia, Kuala Lumpur, Malaysia.
  • Horie R; Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia, Kuantan, Malaysia.
  • Watanabe T; Department of Hematology, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan.
  • Kitamura T; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, and.
  • Ando K; Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
  • Kashiwagi T; Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • Matsui T; Department of Internal Medicine, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo, Japan.
  • Okamoto A; Department of Internal Medicine, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo, Japan.
  • Handa H; Department of Hematology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
  • Kuroda M; Department of Medicine and Clinical Science, Gunma University, Maebashi, Gunma, Japan.
  • Nakamura N; Department of Molecular Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
  • Kotani A; Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Blood ; 131(23): 2552-2567, 2018 06 07.
Article en En | MEDLINE | ID: mdl-29685921
Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Viral / Herpesvirus Humano 4 / Infecciones por Virus de Epstein-Barr / Exosomas / Inflamación / Linfoma Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Blood Año: 2018 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Viral / Herpesvirus Humano 4 / Infecciones por Virus de Epstein-Barr / Exosomas / Inflamación / Linfoma Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Blood Año: 2018 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos