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

• Project/Area Number: 24890270
• Research Category: Grant-in-Aid for Research Activity start-up
• Allocation Type: Single-year Grants
• Research Field: Laboratory medicine
• Research Institution: Suzuka 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: ¥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.

Research Products

• [Journal Article] Kynurenine production mediated by indoleamine 2,3-dioxygenase aggravates liver injury in HBV-specific CTL-induced fulminant hepatitis (2014)
  • 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
  • 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: 3564 Pages: 120-5
  • DOI: 10.1016/j.neulet.2014.01.051
  • 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
  • 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: Journal of Immunology Volume: 15;191(6) Pages: 3057-3064
  • DOI: 10.4049/jimmunol.1203306
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-alpha 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）
  • DOI: 10.1371/journal.pone.0065251
  • Peer Reviewed
• [Journal Article] Remarkable role of indoleamine 2,3-dioxygenase and tryptophan metabolites in infectious diseases : potential role in macrophage-mediated inflammatory diseases (2013)
  • Author(s): Murakami Y, Hoshi M, Imamura Y, Arioka Y, Yamamoto Y, Saito K
  • Journal Title: Mediators of Inflammation Volume: 2013 Pages: 391984-391984
  • DOI: 10.1155/2013/391984
  • 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)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] -Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells (2012)
  • 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/
  • 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 epididymis (2012)
  • Author(s): Fukunaga M, Yamamoto Y, Kawasoe M, Arioka Y, Murakami Y, Hoshi M, Saito K
  • Journal Title: J Histochem Cytochem. Volume: 60(11) Pages: 854-60
  • DOI: 10.1369/0022155412458926
  • Peer Reviewed
• [Journal Article] Pre-administration of L-tryptophan improved ADR-induced early renal failure in mice. (2012)
  • Author(s): Arioka Y
  • Journal Title: Life Sci. Volume: 59 Pages: 100-106
  • DOI: 10.1016/j.lfs.2012.06.018
  • Peer Reviewed
• [Journal Article] Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection (2012)
  • 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) Pages: 245-51
  • DOI: 10.1016/j.cyto.2012.04.022
  • Peer Reviewed
• [Journal Article] High susceptibility to lipopolysaccharide-induced lethal shock in encephalomyocarditis virus-infected mice (2012)
  • Author(s): Ohtaki H
  • Journal Title: Sci Rep Volume: 2 Pages: 367-367
  • DOI: 10.1038/srep00367
  • Peer Reviewed
• [Journal Article] L-tryptophan-kynurenine pathway metabolites regulate type I IFNs of acute viral myocarditis in mice. (2012)
  • Author(s): Hoshi M
  • Journal Title: J Immunol. Volume: 188 Pages: 3980-3987
  • DOI: 10.4049/jimmunol.1100997
  • Peer Reviewed
• [Journal Article] Suppression of azoxymethane-induced colonic preneoplastic lesions in rats by 1-methyltryptophan, an inhibitor of indoleamine 2,3-dioxygenase (2012)
  • 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 Pages: 951-8
  • DOI: 10.1111/j.1349-7006.2012.02237.x
  • Peer Reviewed
• [Presentation] L-Trp administration can be effective in ADR-induced early renal failure through suppressing the TNF-alpha expression (2012)
  • Author(s): Arioka Y
  • Organizer: 13th International Society for Tryptophan Research
  • Place of Presentation: Sydney, Australia
• [Presentation] L-Tryptophan-kynurenine pathway metabolites regulate type I IFNs following viral infections (2012)
  • Author(s): Hoshi M
  • Organizer: 13th International Society for Tryptophan Research
  • Place of Presentation: Sydney, Australia
• [Presentation] Inhibition of IDO activity suppresses Toxoplasma gondii replication and reduces the inflammatory damage in the lung (2012)
  • Author(s): Murakami Y
  • Organizer: 13th International Society for Tryptophan Research
  • Place of Presentation: Sydney, Australia