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The investigation of immune regulation by IDO in NKT cell-mediated immunotherapy

Research Project

Project/Area Number 24890270
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Laboratory medicine
Research InstitutionSuzuka University of Medical Science

Principal Investigator

HOSHI Masato  鈴鹿医療科学大学, 保健衛生学部, 助教 (40633996)

Co-Investigator(Renkei-kenkyūsha) SAITO Kuniaki  京都大学, 医学研究科, 教授 (80262765)
SEISHIMA Mitsuru  岐阜大学, 医学系研究科, 教授 (10171315)
Project Period (FY) 2012-08-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインドールアミン酸素添加酵素 / トリプトファン代謝 / α-ガラクトシルセラミド / NKT細胞免疫療法 / 腫瘍 / IDO / α- ガラクトシルセラミド
Research Abstract

The role of indoleamine 2,3-dioxygenase (Ido) in the L-tryptophan (Trp)-kynurenine (Kyn) pathway after lung metastasis model by injecting B16F10 cells was investigated. We used mice treated with 1-methyl-D or L-tryptophan (D or L-1MT), an inhibitor of Ido1 or Ido2, to study the importance of Trp-Kyn pathway metabolites. On day 7 after B16F10 cells, we administrated each NKT activated ligands (alpha-GalCer and 7DW8-5). The levels of serum IFN-g and Ido activity in mice 6 hours after alpha-GalCer injection were higher than those in non-treated mice. Furthermore, the levels of Ido1 and Ido2 mRNA and protein expression in the lung and serum Trp metabolites from mice treated with alpha-GalCer were significantly higher than those from non-treated mice. Moreover, the anti-tumor effect in the lung from mice treated with alpha-GalCer and D- or L-1MT combined administration was markedly improved compared to that in mice treated with -GalCer single administration.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (19 results)

All 2014 2013 2012

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (3 results)

  • [Journal Article] Kynurenine production mediated by indoleamine 2,3-dioxygenase aggravates liver injury in HBV-specific CTL-induced fulminant hepatitis2014

    • Author(s)
      Ohtaki H, Ito H, Ando K, Ishikawa T, Hoshi M, Ando T, Takamatsu M, Hara A, Moriwaki H, Saito K, Seishima M
    • Journal Title

      Biochim Biophys Acta

      Volume: S0925-4439(14) Pages: 102-1

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indoleamine 2,3-dioxygenase 1 is upregulated in activated microglia in mice cerebellum during acute viral encephalitis2014

    • Author(s)
      Taguchi A, Niwa M, Hoshi M, Saito K, Masutani T, Hisamatsu K, Kobayashi K, Hatano Y, Tomita H, Hara A
    • Journal Title

      Neurosci Lett

      Volume: 3564 Pages: 120-5

    • DOI

      10.1016/j.neulet.2014.01.051

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indoleamine 2,3-dioxygenase 1 is upregulated in activated microglia in mice cerebellum during acute viral encephalitis.2014

    • Author(s)
      Taguchi A, Niwa M, Hoshi M, Saito K, Masutani T, Hisamatsu K, Kobayashi K, Hatano Y, Tomita H, Hara A.
    • Journal Title

      Neurosci Lett

      Volume: 564 Pages: 120-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IDO1 plays an immunosuppressive role in 2, 4, 6-trinitrobenzene sulfate-induced colitis in mice2013

    • Author(s)
      Takamatsu M, Hirata A, Ohtaki H, Hoshi M, Hatano Y, Tomita H, Kuno T, Saito K, Hara A
    • Journal Title

      J Immunol

      Volume: 15;191(6) Issue: 6 Pages: 3057-64

    • DOI

      10.4049/jimmunol.1203306

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor necrosis factor-α promotes cholestasis-induced liver fibrosis in the mouse through tissue inhibitor of metalloproteinase-1 production in hepatic stellate cells.2013

    • Author(s)
      Osawa Y,Saibara T et.al
    • Journal Title

      PloS One

      Volume: 8(6) Issue: 6 Pages: e65251-e65251

    • DOI

      10.1371/journal.pone.0065251

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Remarkable role of indoleamine 2, 3-dioxygenase and tryptophan metabolites in infectious diseases : potential role in macrophage-mediated inflammatory diseases2013

    • Author(s)
      Murakami Y, Hoshi M, Imamura Y, Arioka Y, Yamamoto Y, Saito K
    • Journal Title

      Mediators Inflamm

      Volume: 2013 Pages: 391984-391984

    • DOI

      10.1155/2013/391984

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor necrosis factor-α promotes cholestasis-induced liver fibrosis in the mouse through tissue inhibitor of metalloproteinase-1 production in hepatic stellate cells.2013

    • Author(s)
      Osawa Y, Hoshi M, Yasuda I, Saibara T, Moriwaki H, Kozawa O.
    • Journal Title

      PLoS One

      Volume: 8(6)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] [Indoleamine 2,3-dioxygenase 1 modulates the immuneresponse; the new therapeutic targets of this drug].2013

    • Author(s)
      Yamamoto Y, Murakami Y, Hoshi M, Saito K.
    • Journal Title

      Nihon Yakurigaku Zasshi

      Volume: 142(2) Pages: 85-8

    • NAID

      10031190742

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IDO1 plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate-induced colitis in mice.2013

    • Author(s)
      Takamatsu M, Hirata A, Ohtaki H, Hoshi M, Hatano Y, Tomita H, Kuno T, Saito K, Hara A.
    • Journal Title

      J Immunol

      Volume: 191(6) Pages: 3057-64

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] -Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells2012

    • Author(s)
      Ogawa K, Hara T, Shimizu M, Nagano J, Ohno T, Hoshi M, Ito H, Tsurumi H, Saito K, Seishima M, Moriwaki H
    • Journal Title

      Oncol Lett

      Volume: 4(3) Pages: 546-550

    • URL

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673646/

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Studies on tissue and cellular distribution of indoleamine 2, 3-dioxygenase 2 : the absence of IDO1 upregulates IDO2 expression in the epididymis2012

    • Author(s)
      Fukunaga M, Yamamoto Y, Kawasoe M, Arioka Y, Murakami Y, Hoshi M, Saito K
    • Journal Title

      J Histochem Cytochem

      Volume: 60(11) Issue: 11 Pages: 854-60

    • DOI

      10.1369/0022155412458926

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pre-administration of L-tryptophan improved ADR-induced early renal failure in mice2012

    • Author(s)
      Arioka Y
    • Journal Title

      Life Sci

      Volume: 59 Issue: 3-4 Pages: 100-106

    • DOI

      10.1016/j.lfs.2012.06.018

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of increased indoleamine 2, 3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection2012

    • Author(s)
      Murakami Y, Hoshi M, Hara A, Takemura M, Arioka Y, Yamamoto Y, Matsunami H, Funato T, Seishima M, Saito K
    • Journal Title

      Cytokine

      Volume: 59(2) Issue: 2 Pages: 245-51

    • DOI

      10.1016/j.cyto.2012.04.022

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High susceptibility to lipopolysaccharide-induced lethal shock in encephalomyocarditis virus-infected mice2012

    • Author(s)
      Ohtaki H
    • Journal Title

      Sci Rep.

      Volume: 2 Issue: 1 Pages: 367-375

    • DOI

      10.1038/srep00367

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] L-tryptophan-kynurenine pathway metabolites regulate type 1 IFNs of acute viral myocarditis in mice2012

    • Author(s)
      Hoshi M
    • Journal Title

      J Immunol

      Volume: 188 Issue: 8 Pages: 3980-3987

    • DOI

      10.4049/jimmunol.1100997

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of azoxymethane-induced colonic preneoplastic lesions in rats by 1-methyltryptophan, an inhibitor of indoleamine 2, 3-dioxygenase2012

    • Author(s)
      Ogawa K, Hara T, Shimizu M, Ninomiya S, Nagano J, Sakai H, Hoshi M, Ito H, Tsurumi H, Saito K, Seishima M, Tanaka T, Moriwaki H
    • Journal Title

      Cancer Sci

      Volume: 103 Issue: 5 Pages: 951-958

    • DOI

      10.1111/j.1349-7006.2012.02237.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] L-Trp administration can be effective in ADR-induced early renal failure through suppressing the TNF-alpha expression2012

    • Author(s)
      Arioka Y
    • Organizer
      13th International Society for Tryptophan Research
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2012 Annual Research Report
  • [Presentation] L-Tryptophan-kynurenine pathway metabolites regulate type I IFNs following viral infections2012

    • Author(s)
      Hoshi M
    • Organizer
      13th International Society for Tryptophan Research
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2012 Annual Research Report
  • [Presentation] Inhibition of IDO activity suppresses Toxoplasma gondii replication and reduces the inflammatory damage in the lung2012

    • Author(s)
      Murakami Y
    • Organizer
      13th International Society for Tryptophan Research
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2012 Annual Research Report

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Published: 2012-11-27   Modified: 2019-07-29  

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