The study of amino acids imbalance which influences the immune cells, especially dendritic cells, in patients with advanced cirrhosis.

• Project/Area Number: 21790643
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: KAKAZU Eiji Tohoku University, 病院, 医員 (20509377)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肝硬変 / 分岐鎖アミノ酸 / アミノ酸 / 単球 / 非代償性肝硬変 / xCT / 酸化ストレス / 樹状細胞 / mTOR

Research Abstract

We analyzed the function of myeloid dendritic cells using a serum free culture medium consistent with the average concentration of plasma amino acids from healthy controls or advanced cirrhotic patients to reflect more closely the actual environment of the living body. Elevating the extracellular concentration of BCAAs improved the maturation of dendritic cells in patients with advanced cirrhosis. Elevating the extracellular concentration of BCAAs seems to be beneficial for improving the functions of dendritic cells in advanced cirrhotic patients.

Research Products

• [Journal Article] Lymphotropic HCV strain can infect human primary naive CD4+ cells and affect their proliferation and IFN-γ secretion activity. (2011)
  • Author(s): Kondo Y, Ueno Y, Kakazu E, Kobayashi K, Shiina M, Tamai K, Machida K, Inoue J, Wakui Y, Fukushima K, Obara N, Kimura O, Shimosegawa T.
  • Journal Title: J Gastroenterol. 46(2) Pages: 232-241
  • NAID: 10029027386
  • Peer Reviewed
• [Journal Article] Characterization of the epithelial cell adhesion molecule (EpCAM)+ cell population in hepatocellular carcinoma cell lines. (2010)
  • Author(s): Kimura O, Takahashi T, Ishii N, Inoue Y, Ueno Y, Kogure T, Fukushima K, Shiina M, Yamagiwa Y, Kondo Y, Inoue J, Kakazu E, Iwasaki T, Kawagishi N, Shimosegawa T, Sugamura K.
  • Journal Title: Cancer Sci 101 Pages: 2145-2155
  • NAID: 10027832222
  • Peer Reviewed
• [Journal Article] Hepatitis B virus replication could enhance regulatory T cell activity by producing soluble heat shock protein 60 from hepatocytes. (2010)
  • Author(s): Kondo Y, Ueno Y, Kobayashi K, Kakazu E, Shiina M, Inoue J, Tamai K, Wakui Y, Tanaka Y, Ninomiya M, Obara N, Fukushima K, Ishii M, Kobayashi T, Niitsuma H, Kon S, Shimosegawa T.
  • Journal Title: J Infect Dis 202 Pages: 202-213
  • Peer Reviewed
• [Journal Article] 肝硬変患者の免疫機構に関与する遊離アミノ酸の研究 (2010)
  • Author(s): 嘉数英二
  • Journal Title: 東北医学会雑誌 122巻 Pages: 30-32
• [Journal Article] Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice. (2010)
  • Author(s): Obara N, Fukushima K, Ueno Y, Wakui Y, Kimura O, Tamai K, Kakazu E, Inoue J, Kondo Y, Ogawa N, Sato K, Tsuduki T, Ishida K, Shimosegawa T.
  • Journal Title: J Hepatol 53 Pages: 326-334
  • Peer Reviewed
• [Journal Article] Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. (2010)
  • Author(s): Tamai K, Tanaka N, Nakano T, Kakazu E, Kondo Y, Inoue J, Shiina M, Fukushima K, Hoshino T, Sano K, Ueno Y, Shimosegawa T, Sugamura K.
  • Journal Title: Biochem Biophys Res Commun 399 Pages: 384-390
  • Peer Reviewed
• [Journal Article] Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-gamma ligand (2010)
  • Author(s): Wakui Y, Inoue J, Ueno Y, Fukushima K, Kondo Y, Kakazu E, Obara N, Kimura O, Shimosegawa T.
  • Journal Title: rosiglitazone.Biochem Biophys Res Commun 396 Pages: 508-514
  • Peer Reviewed
• [Journal Article] 肝硬変患者の免疫機構に関与する遊離アミノ酸の研究 (2010)
  • Author(s): 嘉数英二
  • Journal Title: 東北医学会雑誌 Volume: 122巻 Pages: 30-32
• [Journal Article] Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis. (2009)
  • Author(s): Kakazu E, Ueno Y, Kondo Y, Fukushima K, Shiina M, Inoue J, Tamai K, Ninomiya M, Shimosegawa T.
  • Journal Title: Hepatology 50 Pages: 1936-1945
  • Peer Reviewed
• [Journal Article] Sporadic acute hepatitis E occurred constantly during the last decade in northeast Japan. (2009)
  • Author(s): Inoue J, Ueno Y, Nagasaki F, Akahane T, Fukushima K, Kogure T, Kondo Y, Kakazu E, Tamai K, Kido O, Nakagome Y, Ninomiya M, Obara N, Wakui Y, Takahashi M, Okamoto H, Shimosegawa T.
  • Journal Title: J Gastroenterol 44 Pages: 329-337
  • NAID: 10025174367
  • Peer Reviewed
• [Journal Article] 肝硬変でのアミノ酸代謝異常が樹状細胞に与える影響 (2009)
  • Author(s): 嘉数英二, 上野義之, 菅野記豊, 下瀬川徹
  • Journal Title: 肝・胆・膵 58巻2号 Pages: 247-254
• [Journal Article] 非代償性肝硬変で出現する血漿アミノ酸imbalanceは樹状細胞成熟化を抑制し (2009)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 下瀬川徹
  • Journal Title: 分岐鎖アミノ酸(BCAA)により改善する「薬理と治療」 VOL 37 Pages: 93-98
• [Journal Article] 非代償性肝硬変におけるアミノ酸imbalanceが免疫機構に及ぼす影響 (2009)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 下瀬川徹
  • Journal Title: 消化器科 Vol.49 No.2 Pages: 190-196
• [Journal Article] Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis (2009)
  • Author(s): Kakazu E, Ueno Y, Kondo Y, Fukushima K, Shiina M, Inoue J, Tamai K, Ninomiya M, Shimosegawa T.
  • Journal Title: Hepatology 50 Pages: 1936-1945
  • Peer Reviewed
• [Journal Article] 肝硬変でのアミノ酸代謝異常が樹状細胞に与える影響 (2009)
  • Author(s): 嘉数英二, 上野義之, 菅野記豊, 下瀬川徹
  • Journal Title: 肝・胆・膵 58 Pages: 247-254
• [Journal Article] 非代償性肝硬変で出現する血漿アミノ酸 imbalance は樹状細胞成熟化を抑制し、分岐鎖アミノ酸(BCAA)により改善する (2009)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 下瀬川徹
  • Journal Title: 薬理と治療 37 Pages: 93-96
• [Journal Article] 非代償性肝硬変におけるアミノ酸 imbalance が免疫機構に及ぼす影響 (2009)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 下瀬川徹
  • Journal Title: 消化器科 49 Pages: 190-196
• [Presentation] L-CystineはLPS刺激時の単球からのTNF-α産生を高め、非代償性肝硬変の腎機能低下に関与する (2010)
  • Author(s): 嘉数英二
  • Organizer: 第18回日本消化器病関連学会週間
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-10-14
• [Presentation] L-cystineはLPS刺激時の単球からのTNF-α産生を高め (2010)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 福島耕治, 井上淳, 二宮匡史, 涌井祐太, 岩崎隆雄, 下瀬川徹
  • Organizer: 非代償性肝硬変の腎機能低下に関与するJDDW
  • Place of Presentation: 横浜
• [Presentation] Branched-chain amino acids improve the maturation of dendritic cells in patients with advanced cirrhosis ex vivo. (2010)
  • Author(s): EIJI KAKAZU, YOSHIYUKI UENO, YASUTERU KONDO, KOJI FUKUSHIMA, MASAAKI SHIINA YOKO YAMAGIWA, JUN INOUE, KEIICHI TAMAI, NORIYUKI OBARA, OSAMU KIMURA, YUTA WAKUI TOORU SHIMOSEGAWA
  • Organizer: APASL
  • Place of Presentation: 北京
• [Presentation] An imbalance in plasma amino acids of advaced cirrhotic patients impairs the maturation of dendritic cells via mTOR/S6K signaling pathway. (2010)
  • Author(s): EIJI KAKAZU, YOSHIYUKI UENO, YASUTERU KONDO, KOJI FUKUSHIMA, MASAAKI SHIINA, YOKO YAMAGIWA, JUN INOUE, KEIICHI TAMAI, TOORU SHIMOSEGAWA
  • Organizer: APASL
  • Place of Presentation: 香港
• [Presentation] 分岐鎖アミノ酸(BCAA)の樹状細胞成熟化に対する影響とBCAA製剤内服後の血行動態が末梢血単核球に与える影響について (2009)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 福島耕治, 山極洋子, 椎名正明, 井上淳, 玉井恵一, 二宮匡史 城戸治, 中込悠, 小原範之, 木村修, 涌井祐太, 岩崎隆雄, 下瀬川徹
  • Organizer: 肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-05
• [Presentation] 非代償性肝硬変のアミノ酸インバランスが樹状細胞成熟化に及ぼす影響について (2009)
  • Author(s): 嘉数英二
  • Organizer: 肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04