Effect of cyclophilin A in exosome produced by mammary epitheliocyte on bovine mastitis.

• Project/Area Number: 18H02326
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42010:Animal production science-related
• Research Institution: Tohoku University
• Principal Investigator: Aso Hisashi 東北大学, 農学研究科, 教授 (50241625)
• Co-Investigator(Kenkyū-buntansha): 北澤 春樹 東北大学, 農学研究科, 教授 (10204885) ; 奥 夏美 (岡田夏美) 東北大学, 農学研究科, 技術一般職員 (10621584) ; 野地 智法 東北大学, 農学研究科, 教授 (10708001) ; 渡邊 康一 東北大学, 農学研究科, 助教 (80261494)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 牛乳房炎 / シクロフィリンA / エクソソーム / 炎症 / 乳腺免疫 / マイクロアレー解析 / 免疫反応 / シクロフィリンＡ / エクソゾーム / ウシ乳房炎

Outline of Final Research Achievements

Cyclophilin A (CyPA) was originally discovered in bovine thymocytes as a cytosolic binding protein of the immunosuppressive drug cyclosporine A. CyPA is secreted a soluble form and a component in exosome from bovine mammary epithelial cells just before the occurring of mastitis. Exosomes were purified from milk whey of health or mastitis cattle. There were no differences in the size and the CyPA contents of exosomes between health and mastitis cattle. As CyPA in exosome was not measured by ELISA, an increasing CyPA in mastitis milk was a soluble form.

Academic Significance and Societal Importance of the Research Achievements

乳房炎はウシ疾病の中で最も発生率が多く、日本での経済的な損失は年間1000億円と推定される。現在、乳房炎治療の多くが抗生剤を用いた治療を中心に行われており、乳房炎牛の生乳や食肉からのメシチリン耐性黄色ブドウ球菌(MRSA)の検出に加え、食肉と牛乳を介して耐性菌がヒトに伝播した症例が報告された。乳房炎の防除は今日の獣医畜産領域において重大な課題であり、薬剤耐性の発生を回避した新たな予防・診断・治療法等の開発に資する研究が望まれている。よって、シクロフィリンAの乳汁分泌機構および炎症性リンパ球への作用機構を解明して乳房炎病態との関連性を明らかにすることは、乳房炎発症予防・治療への応用へ繋がる。

Research Products

• [Journal Article] The gut microbiota induces Peyer’s-patch-dependent secretion of maternal IgA into milk (2021)
  • Author(s): Usami Katsuki、Niimi Kanae、Matsuo Ayumi、Suyama Yoshihisa、Sakai Yoshifumi、Sato Shintaro、Fujihashi Kohtaro、Kiyono Hiroshi、Uchino Saeka、Furukawa Mutsumi、Islam Jahidul、etc
  • Journal Title: Cell Reports Volume: 36 Issue: 10 Pages: 109655-109655
  • DOI: 10.1016/j.celrep.2021.109655
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of Dietary Supplementation of Immunobiotic Lactiplantibacillusplantarum N14 Fermented Rakkyo (Allium chinense) Pickled Juice on the Immunocompetence and Production Performance of Pigs (2021)
  • Author(s): Islam Md. Aminul、Hashiguchi Kenji、Kober A.K.M. Humayun、Morie Kyoko、Zhou Binghui、Tomokiyo Mikado、Shimazu Tomoyuki、Aso Hisashi、Villena Julio、Suda Yoshihito、Kitazawa Haruki
  • Journal Title: Animals Volume: 11 Issue: 3 Pages: 752-752
  • DOI: 10.3390/ani11030752
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of fat accumulation and adipokine production during the long-term adipogenic differentiation of porcine intramuscular preadipocytes and study of the influence of immunobiotics. (2020)
  • Author(s): Tada, A., Kober, A.H., Islam, M.A., Igata, M., Takagi, M., Suzuki, M., Aso, H., Ikeda-Ohtsubo, W., Yoda, K., Miyazawa, K., He, F., Takahashi, H., Villena, J. and Kitazawa, H.
  • Journal Title: Cells Volume: 9 Issue: 7 Pages: 1715-1715
  • DOI: 10.3390/cells9071715
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] IL-12p40 gene expression in lung and hilar lymph nodes of MPS resistant pigs (2020)
  • Author(s): Akiko Sakuma, Shizuka Sugawara, Hikaru Hidaka, Mitsuru Nakajo, Yoshihito Suda, Tomoyuki Shimazu, Michael T. Rose, Megumi Urakawa, Tao Zhuang, Guoqi Zhao, Kouichi Watanabe, Tomonori Nochi, Haruki Kitazawa, Kazuo Katoh, Keiichi Suzuki, Hisashi Aso
  • Journal Title: Anim. Sci. J. Volume: 91 Issue: 1
  • DOI: 10.1111/asj.13450
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptome Analysis of The Inflammatory Responses of Bovine Mammary Epithelial Cells: Exploring Immunomodulatory Target Genes for Bovine Mastitis (2020)
  • Author(s): Islam, Md. A., T. Michihiro, K. Fukuyama, H. Kitazawa et al.
  • Journal Title: Pathogens Volume: 9:200 Issue: 3 Pages: 1-18
  • DOI: 10.3390/pathogens9030200
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficient Selection of New Immunobiotic Strains With Antiviral Effects in Local and Distal Mucosal Sites by Using Porcine Intestinal Epitheliocytes (2020)
  • Author(s): Leonardo, A., V. Garcia-Castillo, H. Kitazawa et al.
  • Journal Title: Frontiers in Immunology Volume: 11:543 Pages: 1-16
  • DOI: 10.3389/fimmu.2020.00543
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptome modifications in the porcine intramuscular adipocytes during differentiation and exogenous stimulation with TNF-ホア and serotonin. (2020)
  • Author(s): Tada A, Islam MA, Kober HA, Fukuyama K, Takagi M, Igata M, Albarracin L, Ikeda-Ohtsubo W, Miyazawa K, Yoda K, He F, Takahashi H, Villena J, Aso H, Kitazawa H
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 2 Pages: 638-658
  • DOI: 10.3390/ijms21020638
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts (2019)
  • Author(s): Tomoya Takeda, Sota Doiyama, Junya Azumi, Yasuhiro Shimada, Yoshihiko Tokuji, Hiroaki Yamaguchi, Kosuke Nagata, Naoya Sakamoto, Hisashi Aso, Takashi Nakamura
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 13637-13637
  • DOI: 10.1038/s41598-019-49883-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Organogermanium Compound THGP Suppresses Melanin Synthesis via Complex Formation with L-DOPA on Mushroom Tyrosinase and in B16 4A5 Melanoma Cells (2019)
  • Author(s): Azumi Junya、Takeda Tomoya、Shimada Yasuhiro、Aso Hisashi、Nakamura Takashi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 19 Pages: 4785-4797
  • DOI: 10.3390/ijms20194785
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Addition of Wakame seaweed ( Undaria pinnatifida ) stalk to animal feed enhances immune response and improves intestinal microflora in pigs (2019)
  • Author(s): Shimazu Tomoyuki、Borjigin Liushiqi、Katoh Kazuo、Roh Sang‐gun、Kitazawa Haruki、Abe Keietsu、Suda Yoshihito、Saito Hayato、Kunii Hiroshi、Nihei Ken、Uemoto Yoshinobu、Aso Hisashi、Suzuki Keiichi
  • Journal Title: Animal Science Journal Volume: 90 Issue: 9 Pages: 1248-1260
  • DOI: 10.1111/asj.13274
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Isolation and Immunocharacterization of Lactobacillus salivarius from the Intestine of Wakame-Fed Pigs to Develop Novel “Immunosynbiotics” (2019)
  • Author(s): Masumizu, Y., B. Zhou, H. Kitazawa et al.
  • Journal Title: Microorganisms Volume: 7:167 Issue: 6 Pages: 1-17
  • DOI: 10.3390/microorganisms7060167
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptome Modifications in Porcine Adipocytes via Toll-Like Receptors Activation (2019)
  • Author(s): Igata Manami、Islam Md. Aminul、Tada Asuka、Takagi Michihiro、Kober A. K. M. Humayun、Albarracin Leonardo、Aso Hisashi、Ikeda-Ohtsubo Wakako、Miyazawa Kenji、Yoda Kazutoyo、He Fang、Takahashi Hideki、Villena Julio、Kitazawa Haruki
  • Journal Title: Frontiers in Immunology Volume: 10 Pages: 1-15
  • DOI: 10.3389/fimmu.2019.01180
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Paraimmunobiotic Bifidobacteria Modulate the Expression Patterns of Peptidoglycan Recognition Proteins in Porcine Intestinal Epitheliocytes and Antigen Presenting Cells (2019)
  • Author(s): Iida, H., M. Tohno, Md. A. Islam, H. Kitazawa et al.
  • Journal Title: Cells Volume: 8:891 Issue: 8 Pages: 1-22
  • DOI: 10.3390/cells8080891
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Staphylococcus aureus-specific IgA antibody in milk suppresses the multiplication of S. aureus in infected bovine udder (2019)
  • Author(s): Nagasawa Yuya、Kiku Yoshio、Sugawara Kazue、Hirose Aya、Kai Chiaki、Kitano Nana、Takahashi Toshihiko、Nochi Tomonori、Aso Hisashi、Sawada Shin-ichi、Akiyoshi Kazunari、Hayashi Tomohito
  • Journal Title: BMC Veterinary Research Volume: 15 Issue: 1 Pages: 286-286
  • DOI: 10.1186/s12917-019-2025-3
  • NAID: 120006901036
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genomic characterization of Lactobacillus delbrueckii TUA4408L and evaluation of the antiviral activities of its extracellular polysaccharides in porcine intestinal epithelial cells (2018)
  • Author(s): Kanmani, P., L. Albarracin, H. Kobayashi, E. M. Hebert, L. Saavedra, R. Komatsu, B. Gatica, A. S. Burgos, A. Miyazaki, W. Ikeda-Ohtsubo, Y. Suda, H. Aso, S. Egusa, T. Mishima, H. Takahashi, J. Villena, H. Kitazawa
  • Journal Title: Front. Immunol. Volume: 9:2178 Pages: 1-16
  • DOI: 10.3389/fimmu.2018.02178
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of immune and microbial environments is independently regulated in the mammary gland (2018)
  • Author(s): K. Niimi, K. Usami, Y. Fujita, M. Abe, M. Furukawa, Y. Suyama, Y. Sakai, M. Kamioka, N. Shibata, E.J. Park, S. Sato, H. Kiyono, H. Yoneyama, H. Kitazawa, K. Watanabe, T. Nochi and H. Aso
  • Journal Title: Mucosal Immunology Volume: 11 Pages: 643-653
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phenotypic and functional analysis of bovine peripheral blood dendritic cells before parturition by a novel purification method. (2018)
  • Author(s): Zhuang T, Urakawa M, Sato H, Sato Y, Taguchi T, Umino T, Katto S, Tanaka K, Yoshimura K, Takada N, Kobayashi H, Ito M, Rose MT, Kiku Y, Nagasawa Y, Kitazawa H, Watanabe K, Nochi T, Hayashi T, Aso H
  • Journal Title: Anim. Sci. J. Volume: 89 Issue: 7 Pages: 1011-1019
  • DOI: 10.1111/asj.13014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunobiotics for the bovine host: their interaction with intestinal epithelial cells and their effect on antiviral immunity. (2018)
  • Author(s): Julio Villena, Hisashi Aso, Victor P. Rutten, Hideki Takahashi, Willem Van Eden and Haruki Kitazawa
  • Journal Title: Frontiers in Immunology Volume: 9 Pages: 326-326
  • DOI: 10.3389/fimmu.2018.00326
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of a novel mechanism of action of bovine IgG antibodies specific for Staphylococcus aureus (2018)
  • Author(s): Furukawa Mutsumi、Yoneyama Hiroshi、Hata Eiji、Iwano Hidetomo、Higuchi Hidetoshi、Ando Tasuke、Sato Mika、Hayashi Tomohito、Kiku Yoshio、Nagasawa Yuya、Niimi Kanae、Usami Katsuki、Ito Kumiko、Watanabe Kouichi、Nochi Tomonori、Aso Hisashi
  • Journal Title: Veterinary Research Volume: 49 Issue: 1 Pages: 22-22
  • DOI: 10.1186/s13567-018-0517-y
  • NAID: 120006798140
  • Peer Reviewed / Open Access
• [Presentation] シクロフィリンA誘発乳房炎により変化する乳中タンパク質の解析 (2021)
  • Author(s): 秋元 宏介、大崎 雄介、北澤 春樹、麻生 久、白川 仁
  • Organizer: 第11回家畜感染症学会
• [Presentation] ホルスタイン種において乳汁中のIgAおよびIgM濃度の遺伝率は高い (2021)
  • Author(s): 桂哲平・遠藤佑真・庄 涛・浦川めぐみ・吉村 梢・高梨 暁・林 智人・菊 佳男・長澤裕哉・浅野貴史・佐沢公子・横井允雄・吉田 岳・中村武彦・上本吉伸・野地智法・麻生 久
  • Organizer: 第26回日本乳房炎研究会学術集会
• [Presentation] バイオサーファクタント（MEL-B）の有する脂質依存的な黄色ブドウ球菌増殖抑制効果 (2020)
  • Author(s): 山内清哉、山本周平、菅原知宏、曽我部敦、秦英司、古川睦実、米山裕、渡邊康一、麻生久、野地智法
  • Organizer: 第163回日本獣医学会
• [Presentation] 初乳中自然免疫因子Serum Amyloid Aの同定とその作用標的 (2020)
  • Author(s): 内野紗江佳、宇佐美克紀、佐々木志保、新實香奈枝、古川睦実、渡邊康一、麻生久、野地智法
  • Organizer: 第163回日本獣医学会
• [Presentation] 炎症誘起因子シクロフィリンA の乳房炎誘起能の発見 (2019)
  • Author(s): 遠藤佑真・佐藤佑子・小堤知之・浅野貴史・熊谷弘明・吉村 梢・庄 涛・浦川めぐみ・渡邊康一・野地智法・麻生 久
  • Organizer: 第126回日本畜産学会大会
• [Presentation] 離乳直後の腸内の免疫・微生物環境形成に及ぼすパイエル板の役割 (2019)
  • Author(s): 新實香奈枝・宇佐美克紀・古川睦実・馬場柚里・山内清哉・渡邊康一・麻生 久・野地 智法
  • Organizer: 第126回日本畜産学会大会
• [Presentation] 乳汁中のIgA抗体産生を促す腸内微生物の免疫・微生物学的意義 (2019)
  • Author(s): 宇佐美克紀、新實香奈枝、古川睦実、馬場柚里、内野紗江佳、山内清哉、渡邊康一、麻生 久、野地智法
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] 枯草菌を給与した初産牛は炎症状態に陥りにくく健康な状態を維持する (2019)
  • Author(s): 吉村 梢・浦川めぐみ・遠藤佑真・桂 哲平・浅野貴史・熊谷弘明。日野正浩・庄 涛・渡邊康一・野地智法・麻生 久
  • Organizer: 第69回東北畜産学会大会
• [Presentation] プロバイオティクス枯草菌による牛乳房炎発送予防効果 (2019)
  • Author(s): 麻生 久
  • Organizer: 第69回東北畜産学会大会
  • Invited
• [Presentation] Intestinal microflora changes during lactation and has relevance to the specificity of milk IgA and diversity of microflora in the mammary gland (2018)
  • Author(s): Niimi K, Usami K, Furukawa M, Sasaki S, Watanabe K, Aso H, Nochi T.
  • Organizer: Mucosal Immunology Course & Symposium (MICS2018), Oxford, UK
  • Int'l Joint Research
• [Presentation] CCL28-mediated chemotaxis for the recruitment of IgA-producing plasma cells into the mammary gland depends on the lactation-related but not bacterial stimulus (2018)
  • Author(s): Nochi T, Niimi K, Usami K, Furukawa M, Sasaki S, Kiyono H, Watanabe K, Aso H.
  • Organizer: Mucosal Immunology Course & Symposium (MICS2018), Oxford, UK
  • Int'l Joint Research
• [Presentation] シクロフィリンＡの乳頭投与が乳汁中体細胞数に与える影響 (2018)
  • Author(s): 佐藤佑子・吉村 梢・浦川めぐみ・庄 涛・田中孝太朗・遠藤佑真・伊藤 愛・小堤知行・小林宏子・高田直和・渡邊康一・野地智法・麻生 久
  • Organizer: 東北畜産学会第68回大会
• [Presentation] Effect of probiotic Bacillus Subtilis C-3102 strain on function of dendritic cells in bovine peripheral blood before and after parturition (2018)
  • Author(s): Zhuang T, Urakawa M, Sato H, Kobayashi H, Sato Y, Ashida N, Otomo N, Watanabe K, Nochi T, Aso H.
  • Organizer: The 30th World Buiatrics Congress, Sapporo, Japan
  • Int'l Joint Research
• [Presentation] Oral feeding with a probiotics Bacillus subtilis C-3102 modulates the immune and metabolic functions in dairy cattle, resulting in prevention of mastitis (2018)
  • Author(s): Urakawa M, Sato H, Zhuang T, Taguchi T, Katto S, Tanaka K, Kobayashi H, Ito M, Sato Y, Ashida N, Otomo N, Watanabe K, Nochi T, Aso H.
  • Organizer: The 30th World Buiatrics Congress, Sapporo, Japan
  • Int'l Joint Research
• [Presentation] ウシ乳房炎誘起因子シクロフィリンＡの乳汁における存在様式 (2018)
  • Author(s): 吉村 梢・海野 剛・浦川めぐみ・庄 涛・田中孝太朗・遠藤佑真・佐藤佑子・小堤知行・佐藤秀俊・渡邊康一・野地智法・麻生 久
  • Organizer: 日本獣医学会第161回大会
• [Presentation] パイエル板から乳腺に遊走するIgA産生細胞の同定 (2018)
  • Author(s): 宇佐美克紀・新實香奈枝・佐々木志保・馬場柚里・古川睦実・伊藤 駿・渡邊康一・麻生 久・野地智法
  • Organizer: 日本獣医学会第161回大会
• [Presentation] 早期診断法開発とプロバイオティクス飼料による乳房炎発症制御 (2018)
  • Author(s): 麻生 久
  • Organizer: 第49回日本家畜臨床学会
  • Invited
• [Book] 獣医組織学 第８版 (2020)
  • Author(s): 渡邊康一、麻生 久
  • Total Pages: 397
  • Publisher: 学窓社
  • ISBN: 9784873627731
• [Remarks] 東北大学大学院農学研究科 家畜健康科学寄附講座
  • URL: https://www.agri.tohoku.ac.jp/keitai/info/health-science.html
• [Remarks] 東北大学大学院農学研究科 動物機能形態学分野
  • URL: https://www.agri.tohoku.ac.jp/keitai/index.html
• [Remarks] 東北大学大学院農学研究科 食と農免疫研究教育センター
  • URL: https://www.agri.tohoku.ac.jp/cfai/index.html
• [Remarks] 研究拠点形成事業 先端拠点形成
  • URL: https://www.agri.tohoku.ac.jp/fain/index.html
• [Remarks] 東北大学大学院農学研究科 機能形態学分野
  • URL: http://www.agri.tohoku.ac.jp/keitai/index-j.html
• [Remarks] 東北大学大学院農学研究科 食と農免疫研究教育センター
  • URL: http://www.agri.tohoku.ac.jp/cfai/index.html
• [Remarks] 研究拠点形成事業 先端拠点形成
  • URL: http://www.agri.tohoku.ac.jp/fain/index.html
• [Remarks] 東北大学大学院農学研究科 機能形態学分野
  • URL: http://www.agri.tohoku.ac.jp/keitai/index-j.html
• [Remarks] 東北大学大学院農学研究科 食と農免疫研究教育センター
  • URL: http://www.agri.tohoku.ac.jp/cfai/index.html
• [Remarks] 研究拠点形成事業 先端拠点形成
  • URL: http://www.agri.tohoku.ac.jp/fain/index.html