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Immunomodulatory effects ofB cell derivedVEGF-A in mice

Research Project

Project/Area Number 22390179
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKagoshima University

Principal Investigator

HASHIGUCHI Teruto  鹿児島大学, 大学院・医歯学総合研究科, 教授 (70250917)

Co-Investigator(Kenkyū-buntansha) KAWAHARA Koichi  大阪工業大学, 工学部, 特任教授 (10381170)
MARUYAMA Ikuro  鹿児島大学, 大学院・医歯学総合研究科, 特任教授 (20082282)
ITO Takashi  鹿児島大学, 大学院・医歯学総合研究科, 特任講師 (20381171)
OYAMA Yoko  鹿児島大学, 医学部・歯学部付属病院, 特任助教 (20583470)
SHIMIZU Toshiaki  鹿児島大学, 大学院・医歯学総合研究科, 助教 (50468055)
Co-Investigator(Renkei-kenkyūsha) TAKENOUCHI Kazunori  鹿児島大学, 医学部・歯学部付属病院, 医員 (30646758)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2010: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords神経 / 免疫 / VEGF / リンパ節 / B細胞 / 高内皮小静脈 / LPS tolerance / B cell / immune / lymph / spleen / iron / HEV / angiogenesis / VEGF-A / POEMS syndrome / immune system / nervus system / lymph node / high endothelial venule / mouse
Research Abstract

Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recentstudies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19Cre/hVEGF-Afl) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses. 交付決定額

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (39 results)

All 2012 2011 2010

All Journal Article (22 results) (of which Peer Reviewed: 21 results) Presentation (5 results) Book (3 results) Patent(Industrial Property Rights) (9 results) (of which Overseas: 3 results)

  • [Journal Article] Paucity of CD34-positive cells and increased expression of high-mobility group box 1 in coronary thrombus with type 2 diabetes mellitus2012

    • Author(s)
      Yamashita A, Nishihira K, Matsuura Y, Ito T, Kawahara K, Hatakeyama K, Hashiguchi T, Maruyama I, Yagi H, Matsumoto M, Fujimura Y, Kitamura K, Shibata Y, Asada Y.
    • Journal Title

      Atherosclerosis

      Volume: 224(2) Pages: 511-514

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial growth factor corrected for platelet count and hematocrit is associated with the clinical course of aplastic anemia in children2012

    • Author(s)
      Kodama Y, Okamoto Y, Hashiguchi T, Shinkoda Y, Nishikawa T, Tanabe T, Kawano Y
    • Journal Title

      Int J Hematol

      Volume: 95(5) Pages: 494-499

    • NAID

      10030633031

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of esophagus detection by three-dimensional electroanatomical mapping to avoid esophageal injury during ablation of atrial fibrillation2012

    • Author(s)
      Maenosono R, Oketani N, Ishida S, Iriki Y, Ichiki H, Okui H, Ninomiya Y, Hamasaki S, Namino F, Matsushita M, Tei C, Hashiguchi T.
    • Journal Title

      J Cardiol

      Volume: 60(2) Pages: 119-125

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] MK615, a Prunus mume Steb. Et Zucc ('Ume') extract, attenuates the growth of A375 melanoma cells by inhibiting the ERK1/2-Id-1 pathway2012

    • Author(s)
      Tada K, Kawahara K, Matsushita S, Hashiguchi T, Maruyama I, Kanekura T
    • Journal Title

      Phytother Res

      Volume: 26(6) Pages: 833-838

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] MK615, a Prunus mume Steb.Et Zucc (Ume) extract, attenuates the growth of A375 melanoma cells by inhibiting the ERK1/2-Id-1 pathway2012

    • Author(s)
      Tada K
    • Journal Title

      Phytother Res

      Volume: (in press) Issue: 6 Pages: 833-838

    • DOI

      10.1002/ptr.3645

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of esophagus detection by three-dimensional electroanatomical mapping to avoid esophageal injury during ablation of atrial fibrillation.2012

    • Author(s)
      Maenosono R
    • Journal Title

      J Cardiol

      Volume: 60 Issue: 2 Pages: 119-125

    • DOI

      10.1016/j.jjcc.2012.02.009

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial growth factor corrected for platelet count and hematocrit is associated with the clinical course of aplastic anemia in children2012

    • Author(s)
      Kodama Y, et al
    • Journal Title

      Int J Hematol

      Volume: (In press) Issue: 5 Pages: 494-499

    • DOI

      10.1007/s12185-012-1074-1

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease2011

    • Author(s)
      Oda K, Ido A, Tamai T, Matsushita M, Kumagai K, Mawatari S, Saishoji A, Kure T, Ohno K, Toyokura E, Imanaka D, Moriuchi A, Uto H, Oketani M, Hashiguchi T, Tsubouchi H
    • Journal Title

      Oncol Rep

      Volume: 26(5) Pages: 1227-1233

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intravitreous VEGF-A in eyes with massive vitreous hemorrhage2011

    • Author(s)
      Shirasawa M, Arimura N, Otsuka H, Sonoda S, Hashiguchi T, Sakamoto T
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol

      Volume: 249(12) Pages: 1805-1810

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] NSAIDs inhibit neovascularization of choroid through HO-1-dependent pathway2011

    • Author(s)
      Yoshinaga N, Arimura N, Otsuka H, Kawahara K, Hashiguchi T, Maruyama I, Sakamoto T
    • Journal Title

      Lab Invest

      Volume: 91(9) Pages: 1277-1290

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative peptidomic analysis by a newly developed one-step direct transfer technology without depletion of major blood proteins: its potential utility for monitoring of pathophysiological status in pregnancy-induced hypertension2011

    • Author(s)
      Araki Y, Nonaka D, Tajima A, Maruyama M, Nitto T, Ishikawa H, Yoshitake H, Yoshida E, Kuronaka N, Asada K, Yanagida M, Nojima M, Yoshida K, Takamori K, Hashiguchi T, Maruyama I, Lee LJ, Tanaka K
    • Journal Title

      Proteomics.

      Volume: 11(13) Pages: 2727-2737

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) strains from patients with orthopaedic device-related infections2011

    • Author(s)
      Kawamura H, Nishi J, Imuta N, Tokuda K, Miyanohara H, Hashiguchi T, Zenmyo M, Yamamoto T, Ijiri K, Kawano Y, Komiya S
    • Journal Title

      FEMS Immunol Med Microbiol

      Volume: 63(1) Pages: 10-15

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease2011

    • Author(s)
      Oda K, Hashiguchi T, 15番目, et al
    • Journal Title

      Oncol Rep

      Volume: 26 Pages: 1227-1233

    • DOI

      10.3892/or.2011.1425

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravitreous VEGF-A in eyes with massive vitreous hemorrhage2011

    • Author(s)
      Shirasawa M, Hashiguchi T, 5番目, et al
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol

      Volume: 249 Pages: 1805-1810

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NSAIDs inhibit neovascularization of choroid through HO-1-dependent pathway2011

    • Author(s)
      Yoshinaga N, Arimura N, Otsuka H, Kawahara K, Hashiguchi T, Maruyama I, Sakamoto T.
    • Journal Title

      Lab Invest

      Volume: 91(9) Issue: 9 Pages: 1277-1290

    • DOI

      10.1038/labinvest.2011.101

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of biofilm formation of methicillin-resistant Staphylococcus aureus (MESA) strains from patients with orthopaedic device-related infections2011

    • Author(s)
      Kawamura H, Nishi J, Imuta N, Tokuda K, Miyanohara H, Hashiguchi T, Zenmyo M, Yamamoto T, Ijiri K, Kawano Y, Komiya S
    • Journal Title

      FEMS Immunology & Medical Microbiology

      Volume: 63 Issue: 1 Pages: 10-15

    • DOI

      10.1111/j.1574-695x.2011.00821.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管機能とアイドリング2011

    • Author(s)
      橋口照人
    • Journal Title

      日本血栓止血学会誌

      Volume: 22 Pages: 11-17

    • NAID

      10031162916

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Stromal cell-derived factor-1 is essential for photoreceptor cell protection in retinal detachment2010

    • Author(s)
      Otsuka H, Arimura N, Sonoda S, Nakamura M, Hashiguchi T, Maruyama I, Nakao S, Hafezi-Moghadam A, Sakamoto T
    • Journal Title

      Am J Pathol

      Volume: 177 (5) Pages: 2268-2277

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Advanced malignant melanoma responds to Prunus mume Sieb. Et Zucc (Ume) extract: Case report and in vitro study.2010

    • Author(s)
      Matsushita S, Tada KI, Kawahara KI, Kawai K, Hashiguchi T, Maruyama I, Kanekura T
    • Journal Title

      Exp Ther Med

      Volume: 1(4) Pages: 569-574

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB2010

    • Author(s)
      Mera K, Kawahara K, Tada K, Kawai K, Hashiguchi T, Maruyama I, Kanekura T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 397(2) Pages: 350-354

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB.2010

    • Author(s)
      Mera K, Hashiguchi T (5^<th>), et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 397 Pages: 350-354

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stromal cell-derived factor-1 is essential for photoreceptor cell protection in retinal detachment.2010

    • Author(s)
      Otsuka H, Hashiguchi T (5^<th>), et al.
    • Journal Title

      The American Journal of Pathology

      Volume: 177 Pages: 2268-2277

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 内臓平滑筋 human VEGF-A 発現マウスにおける膵インスリン陽性細胞の構築変化2012

    • Author(s)
      竹之内和則、永里 朋香、清水 利明、丸山 征郎、橋口 照人
    • Organizer
      第59回日本臨床検査医学会学術集
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] 免疫B細胞発現VEGF-Aによるリンパ節リモデリングと免疫環境の機能的制2012

    • Author(s)
      橋口照人、伊藤隆史、SHRESTHA B、三浦直樹、丸山征郎
    • Organizer
      第34回日本血栓止血学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] 免疫B 細胞発現VEGF-A によるリンパ節リモデリングと免疫環境の機能的制御2012

    • Author(s)
      橋口照人
    • Organizer
      第34回 日本血栓止血学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Clinicopathological Conferenceコメンテーター2011

    • Author(s)
      橋口照人
    • Organizer
      第58回日本臨床検査医学会学術集会
    • Place of Presentation
      岡山(招待講演)
    • Year and Date
      2011-11-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生体内ペプチド断片の多様性とゆらぎ~検査医学の新たな視点として~2011

    • Author(s)
      橋口照人
    • Organizer
      第33回日本薬学会九州支部コロキウム
    • Place of Presentation
      鹿児島(招待講演)
    • Year and Date
      2011-10-29
    • Related Report
      2011 Annual Research Report
  • [Book] 医薬ジャーナル2012

    • Author(s)
      橋口照人、清水利昭、竹之内和則
    • Total Pages
      7
    • Publisher
      新しい抗凝固薬・抗血小板薬
    • Related Report
      2011 Annual Research Report
  • [Book] 日本血栓止血学会誌2011

    • Author(s)
      橋口照人
    • Total Pages
      7
    • Publisher
      血管機能とアイドリング
    • Related Report
      2011 Annual Research Report
  • [Book] 医学のあゆみ2011

    • Author(s)
      橋口照人
    • Total Pages
      3
    • Publisher
      NETosisとDIC
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] がん転移マーカーおよびそれを用いた診断2012

    • Inventor(s)
      橋口 照人 夏越祥次 佐々木 健 奥村 浩 内門泰斗 竹之内和則 清水利昭 田中憲次 李 良子 野中大輔
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Industrial Property Number
      2012-168064
    • Filing Date
      2012-07-30
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] がん転移マーカーおよびそれを用いた診断2012

    • Inventor(s)
      夏越祥次 橋口照人 他
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-168064
    • Filing Date
      2012-07-30
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] N結合型糖鎖を利用した消化器癌の検査方法2012

    • Inventor(s)
      夏越祥次 橋口照人 他
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-10-05
    • Related Report
      2012 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 消化器癌診断用マーカー、および消化器癌の検査方法2011

    • Inventor(s)
      橋口 照人 夏越祥次 内門泰斗 新地洋之 前村公成 又木雄弘 森脇紀親 関島 勝 島岡秀行 阿部 碧 福島雅夫 五十嵐幸太 阿部皓基 相原大和
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Industrial Property Number
      2011-222353
    • Filing Date
      2011-10-06
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 消化器癌診断用マーカー、および消化器癌の検査方法2011

    • Inventor(s)
      橋口 照人 夏越祥次 内門泰斗 新地洋之 前村公成 又木雄弘 森脇紀親 関島 勝 島岡秀行 阿部 碧 福島雅夫 五十嵐幸太 阿部皓基 相原大和
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Filing Date
      2011-10-06
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 糖尿病性腎症患者の病態把握方法2011

    • Inventor(s)
      橋口照人 谷口尚太郎 丸山征郎 小野智子 古崎文雄
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Acquisition Date
      2011-11-25
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] N結合型糖鎖を利用した消化器癌の検査方法2010

    • Inventor(s)
      橋口 照人 夏越祥次 内門泰斗 新地洋之 前村公成 又木雄弘 森脇紀親 関島 勝 島岡 秀行 阿部 碧
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Industrial Property Number
      2012-509688
    • Filing Date
      2010-04-06
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] N結合型糖鎖を利用した消化器癌の検査方法2010

    • Inventor(s)
      橋口 照人 夏越祥次 内門泰斗 新地洋之 前村公成 又木雄弘 森脇紀親 関島 勝 島岡 秀行 阿部 碧
    • Industrial Property Rights Holder
      鹿児島大学 他
    • Filing Date
      2010-04-06
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] N結合型糖鎖を利用した消化器癌の判定方法2010

    • Inventor(s)
      夏越祥次、橋口照人, 他4名
    • Industrial Property Rights Holder
      鹿児島大学、住友ベークライト株式会社、三菱化学メディエンス株式会社
    • Industrial Property Number
      2010-088089
    • Filing Date
      2010-04-06
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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