Increases in Tryptophan-kynurenine pathway metabolism following interferon-induced depression

• Project/Area Number: 23390149
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kyoto University
• Principal Investigator: SAITO KUNIAKI 京都大学, 医学(系)研究科(研究院), 教授 (80262765)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Yasuko 京都大学, 大学院・医学研究科, 助教 (00331869) ; MURAKAMI Yuki 京都大学, 大学院・医学研究科, 研究員 (50580106) ; 竹田 真由 東北福祉大学, 健康科学部, 助手 (00423054)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2011: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: サイトカイン / インターフェロン / トリプトファン / IDO / 抑うつ / ウイルス性肝炎 / コンパニオン診断 / 病態検査学 / 酵素誘導 / うつ病

Research Abstract

Increases in L-tryptophhn (TRP) to L-kynurenine (KYN) pathway metabolism were found in interferon (IFN) treated-HCV patients with depressive symptoms. Further, mice with Interferon (IFN) gene transfection induced indoleamine 2,3-dioxygenase (IDO1) , resulting marked increase in TRP to KYN pathway metabolites, which well correlated with depression. The blockade of IDO1 activation prevented the development of depressive-like behavior.

Research Products

• [Journal Article] Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme. (2014)
  • Author(s): Yamamoto R, Yamamoto Y, Imai S, Fukutomi R, Ozawa Y, Abe M, Matuo Y, Saito K
  • Journal Title: PLoS One Volume: 12;9(2)
  • DOI: 10.1371/journal.pone.0088789
  • Peer Reviewed
• [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: 1842(9) Pages: 1464-71
  • DOI: 10.1016/j.bbadis.2014.04.015
  • Peer Reviewed
• [Journal Article] Induction of HBsAg-specific cytotoxic T lymphocytes can be up-regulated by the inhibition of indoleamine 2, 3-dioxygenase activity (2014)
  • Author(s): Ito H, Ando T, Ando K, Ishikawa T, Saito K, Moriwaki H, Seishima M
  • Journal Title: Immunology
  • DOI: 10.1111/imm.12274
  • Peer Reviewed
• [Journal Article] Effects of indoleamine 2,3-dioxygenase deficiency on high-fat diet-induced hepatic inflammation. (2013)
  • Author(s): Nagano J, Shimizu M, Hara T, Shirakami Y, Kochi T, Nakamura N, Ohtaki H, Ito H, Tanaka T, Tsurumi H, Saito K, Seishima M, Moriwaki H
  • Journal Title: PLoS One Volume: 9;8(9)
  • DOI: 10.1371/journal.pone.0073404
  • 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] 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] Species and cell types difference in tryptophan metabolism (2013)
  • Author(s): Murakami Y, Saito K
  • Journal Title: Int J Tryptophan Res Volume: 21;6 Pages: 47-54
  • DOI: 10.4137/ijtr.s11558
• [Journal Article] Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2. (2013)
  • Author(s): Kawasoe M, Yamamoto Y, Okawa K, Funato T, Takeda M, Hara T, Tsurumi H, Moriwaki H, Arioka Y, Takemura M, Matsunami H, Markey SP, Saito K.
  • Journal Title: Exp Hematol. Volume: 41(7) Pages: 597-603
  • DOI: 10.1016/j.exphem.2013.03.004
  • 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
• [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] 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] 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] Posttranslational modification of indoleamine 2, 3-dioxygenase (2012)
  • Author(s): Fujigaki H, Seishima M, Saito K
  • Journal Title: Anal Bioanal Chem Volume: 403(7) Pages: 1777-82
  • DOI: 10.1007/s00216-012-5946-2
• [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] L-Tryptophan-kynurenine pathway metabolites regulate type I IFNs of acute viral myocarditis in mice (2012)
  • Author(s): Hoshi M, Yamamoto Y, Saito K, 他4名
  • Journal Title: J Immunol Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Posttranslational modification of indoleamine 2,3-dioxygenase (2012)
  • Author(s): Fujigaki H, Seishima M, Saito K
  • Journal Title: Anal Bioanal Chem Volume: (印刷中)
  • Peer Reviewed
• [Presentation] Recent advances of biomarker discovery in biological fluids by using Mass Spec trometry (2013)
  • Author(s): Saito, K
  • Organizer: 8th International Conference of Clinica l Laboratory Automation
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] Labdane-type diterpene, constituent from myoga which are traditional Japanese food inhibit enzyme activity and gene expression of in doleamine 2, 3-dioxygenase 1 (2013)
  • Author(s): Imai, R Yamamoto, Y Yamamoto, Y Katayan agi, R Fukutomi, M Abe, Y Ozawa, K Saito
  • Place of Presentation: Milan, Italy
• [Presentation] 疾患メタボローム・疾患プロテオミクス解析 (2013)
  • Author(s): 斉藤邦明
  • Place of Presentation: 仙台市
• [Presentation] 免疫調節因子インドールアミン 2, 3-ジオキシゲナーゼ1の新規阻害剤探索 : フィトケミカルを中心として (2013)
  • Author(s): 山本梨絵, 山本康子, 今井伸二郎, 松尾雄志, 小澤好夫, 阿部雅子, 福富竜太, 斉藤邦明
  • Organizer: 第36回日本分子生物学会年会
• [Presentation] Labdane-type diterpene, constituent from myoga which are traditional Japanese food inhibit enzyme activity and gene expression of indoleamine 2,3-dioxygenase 1 (2013)
  • Author(s): S Imai, R Yamamoto, Y Yamamoto, Y Katayanagi, R Fukutomi, M Abe, Y Ozawa, K Saito
  • Organizer: 15thInternational Congress of Immunology
  • Place of Presentation: Milan, Italy
• [Presentation] 免疫調節因子インドールアミン 2,3-ジオキシゲナーゼ1の新規阻害剤探索：フィトケミカルを中心として (2013)
  • Author(s): 山本梨絵, 山本康子, 今井伸二郎, 松尾雄志, 小澤好夫, 阿部雅子, 福富竜太, 斉藤邦明
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Species and cell types differences in L-tryptophan metabolism (2012)
  • Author(s): Murakami Y
  • Organizer: 13th International Society for Tryptophan Research Conference Satellite Symposium
  • Place of Presentation: Brisbane, Australia
  • Invited
• [Presentation] Recent advances of biomarker discovery in biological fluids by using Mass Spectrometry (2012)
  • Author(s): Saito K
  • Organizer: 8th International Conference of Clinical Laboratory Automation
  • Place of Presentation: Seoul, Korea
  • Invited
• [Book] :Tumor Necrosis factor (2014)
  • Author(s): Murakami Y, Imamura Y, Mitani S, Hoshi M, Arioka Y, Yamamoto Y, Seiyama A, Saito K.
  • Publisher: Nova Science Publishers, Inc.
• [Book] Tumor Necrosis Factor-alpha Related Signal Pathways and Neuronal Diseases (2013)
  • Author(s): Murakami Y
  • Total Pages: 28
  • Publisher: Nova Science Publishers, Inc.
• [Book] Tumor Necrosis factor
  • Author(s): Murakami Y, Imamura Y, Mitani S, Hoshi M, Arioka Y, Yamamoto Y, Seiyama A, Saito K
  • Publisher: Nova Science Publishers, Inc
• [Remarks]
  • URL: http://www.saito-lab-kyotouniv.com
• [Remarks] ホームページ
  • URL: http://www.saito-lab-kyotouniv.com
• [Remarks]
  • URL: http://www.hs.med.kyoto-u.ac.jp/saito-k/index.html
• [Patent(Industrial Property Rights)] 関節リューマチ患者における生物学的製剤の有効性の予測方法 (2013)
  • Inventor(s): 斉藤邦明, 坪井彩, 山本康子
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 2013-127092
  • Filing Date: 2013-06-18
  • Application Year: 2013