The plasma L-Cystine / L-Glutamate imbalance in cirrhosis influences the function of antigen-presenting cell.

• Project/Area Number: 23790762
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: KAKAZU Eiji 東北大学, 東北メディカル・メガバンク機構, 助教 (20509377)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 血漿アミノ酸不均衡 / 非代償性肝硬変 / 単球 / 腎機能障害 / L-シスチン / アミノ酸 / 肝硬変 / 免疫 / L-グルタミン酸 / アミノ酸不均衡

Research Abstract

We demonstrated for the first time that an L-Cys/L-Glu imbalance, especially high levels of L-Cys, increases pro-inflammatory cytokines, especially TNF-alpha from peripheral CD14+ monocytes under the amino acid condition of advanced cirrhosis in vitro, and these results are consistent with the relationships among plasma L-Cys and TNF-alpha in patients with advanced cirrhosis. This study may provide a new approach for future studies to ameliorate the immune dysfunction in patients with advanced cirrhosis.

Research Products

• [Journal Article] Eradication ofhepatitis C virus (HCV) could improve the immunological status and pyoderma gangrenosum-like lesion (2013)
  • Author(s): Kondo Y, Iwata T, Haga T, Kimura O, Ninomiya M, Kakazu E, Kogure T, Morosawa T, Aiba S, Shimosegawa T.
  • Journal Title: Hepatology Research Volume: 44 Issue: 2 Pages: 4-4
  • DOI: 10.1111/hepr.12102
  • Peer Reviewed
• [Journal Article] Hepatitis B surface antigen could contribute to the immunopathogenesis of hepatitis B virus infection. (2013)
  • Author(s): Yasuteru Kondo et al.
  • Journal Title: ISRN Gastroenterol. Volume: 2013:935295 Pages: 935295-935295
  • DOI: 10.1155/2013/935295
  • Peer Reviewed
• [Journal Article] Relationship between renal dysfunction and abnormalities of the immune system in patients with decompensated cirrhosis (2012)
  • Author(s): Kakazu E, Kondo Y, Shimosegawa T
  • Journal Title: ISRN Gastroenterology Volume: 2012 Pages: 123826-123826
  • DOI: 10.5402/2012/123826
  • Peer Reviewed
• [Journal Article] Association between S21 substitution in the core protein of hepatitis B virus and fulminant hepatitis. (2012)
  • Author(s): Jun Inoue et al.
  • Journal Title: J Clin Virol. Volume: 55(2) Issue: 2 Pages: 147-152
  • DOI: 10.1016/j.jcv.2012.06.011
  • Peer Reviewed
• [Journal Article] Use of illumina deep sequencing technology to differentiate hepatitis Cvirus variants (2012)
  • Author(s): Ninomiya M, Ueno Y, Funayama R, Kagashima T, Nishida Y, Kondo Y, Inoue J, Kakazu E, Kimura O, Nakayama K, Shimosegawa T
  • Journal Title: Journal of clinical microbiology Volume: 50 Issue: 3 Pages: 857-866
  • DOI: 10.1128/jcm.05715-11
  • Peer Reviewed
• [Journal Article] Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway (2012)
  • Author(s): Tamai K, Shiina M, Tanaka N, Nakano T, Yamamoto A, Kondo Y, Kakazu E, Inoue J, Fukushima K, Sano K, Ueno Y, Shimosegawa T, Sugamura K.
  • Journal Title: Virology Volume: 22(2) Issue: 2 Pages: 377-85
  • DOI: 10.1016/j.virol.2011.11.009
  • Peer Reviewed
• [Journal Article] Sequential Immunological Analysis of HBV/HCV Co-Infected Patients During (2012)
  • Author(s): Kondo Y, Ueno Y, Ninomiya M, Tamai K, Tanaka Y, Inoue J, Kakazu E, Kobayashi K, Shimosegawa T
  • Journal Title: Peg-IFN/RBV therapy J Gastroenterol Volume: 47(12) Issue: 12 Pages: 1323-35
  • DOI: 10.1007/s00535-012-0596-x
  • Peer Reviewed
• [Journal Article] 非代償性肝硬変における腎機能低下の要因 (2012)
  • Author(s): 嘉数英二、近藤泰輝、二宮匡史、木村修、下瀬川徹
  • Journal Title: 消化器内科 Volume: 54(3) Pages: 380-385
  • Peer Reviewed
• [Journal Article] The influence of pioglitazone on the plasma amino acids profile in patients with Nonalcoholic Steatohepatitis (NASH) (2012)
  • Author(s): Kakazu E, Kondo Y, Ninomiya M, Kimura O, Nagasaki F, Ueno Y, Shimosegawa T.
  • Journal Title: Hepatology International Volume: 2012 Issue: 2 Pages: 577-585
  • DOI: 10.1007/s12072-012-9395-y
  • Peer Reviewed
• [Journal Article] 非代償性肝硬変における腎機能低下の要因 (2012)
  • Author(s): 嘉数英二
  • Journal Title: 消化器内科 Volume: Vol.54 No.3 Pages: 380-385
• [Journal Article] The Nutritional Index 'CONUT' Is Useful for Predicting Long-Term Prognosis of Patients with End-Stage Liver Diseases (2011)
  • Author(s): Fukushima, K., Ueno, Y., Kawagishi, N., Kondo, Y., Inoue, J., Kakazu, E., Ninomiya, M., Wakui, Y., Saito, N., Satomi, S., and Shimosegawa, T.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 224 Issue: 3 Pages: 215-219
  • DOI: 10.1620/tjem.224.215
  • NAID: 10029051173
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Enhanced replication of hepatitis B virus with frameshift in the precore region found in fulminant hepatitis patients (2011)
  • Author(s): Inoue, J., Ueno, Y., Wakui, Y., Fukushima, K., Kondo, Y., Kakazu, E., Ninomiya, M., Niitsuma, H., and Shimosegawa, T.
  • Journal Title: The Journal of infectious diseases Volume: 204 Issue: 7 Pages: 1017-1025
  • DOI: 10.1093/infdis/jir485
  • Peer Reviewed
• [Journal Article] Plasma L-cystine/L-glutamate imbalance increases tumor necrosis factor-alpha from CD14+circulating monocytes in patients with advanced cirrhosis (2011)
  • Author(s): E. Kakazu, Y. Ueno, Y. Kondo, J. Inoue, M. Ninomiya, O. Kimura, Y. Wakui, K. Fukushima, K. Tamai, T. Shimosegawa
  • Journal Title: PLoS One Volume: 6 Issue: 8 Pages: 23402-23402
  • DOI: 10.1371/journal.pone.0023402
  • Peer Reviewed
• [Journal Article] Rapid Reduction of HCV-Core protein in the peripheral blood improve the immunological response in Chronic Hepatitis C patients (2011)
  • Author(s): Yasuteru Kondo, Yoshiyuki Ueno, Yuta Wakui et al.
  • Journal Title: Hepatology Research Volume: 41(12) Issue: 12 Pages: 1153-1168
  • DOI: 10.1111/j.1872-034x.2011.00878.x
  • Peer Reviewed
• [Journal Article] Plasma L-Cystine / L-Glutamate imbalance increases tumor necrosis factor-alpha from CD14+ circulating monocytes in patients with advanced cirrhosis. (2011)
  • Author(s): Kakazu E, Ueno Y, Kondo Y, Inoue J, Ninomiya M, Kimura O, Wakui Y, Fukushima K, Tamai K, Shimosegawa T.
  • Journal Title: PLoS One Volume: 6(8)
  • Peer Reviewed
• [Journal Article] 肝硬変に出現する血漿アミノ酸不均衡が免疫機構に与える影響について (2011)
  • Author(s): 嘉数英二 上野義之 下瀬川徹
  • Journal Title: 肝胆膵 Volume: 63(3) Pages: 375-382
• [Presentation] The influence of pioglitazone on the plasma amino acids profile in patients with nonalcoholic steatohepatitis (NASH). (2012)
  • Author(s): 嘉数英二
  • Organizer: 第４８回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] Pioglitazoneの非アルコール性脂肪性肝炎（NASH）に対する治療効果と血漿アミノ酸濃度に与える影響 (2012)
  • Author(s): 嘉数英二
  • Organizer: 第20回 日本消化器関連学会週間
  • Place of Presentation: 東京
• [Presentation] The influence of pioglitazone on the plasma amino acids profile in patients with nonalcoholic steatohepatitis (NASH). (2012)
  • Author(s): Eiji Kakazu
  • Organizer: The American Association for the Study of Liver Diseases (AASLD) anual meeting
  • Place of Presentation: boston, USA
• [Presentation] An imbalance in plasma amino acids of advanced cirrhotic patients suppresses the maturation of dendritic cells by reducing the intracellular ATP due to interference with the mitochondrial TCA cycle. (2012)
  • Author(s): Eiji Kakazu
  • Organizer: The American Association for the Study of Liver Diseases (AASLD) anual meeting
  • Place of Presentation: boston, USA
• [Presentation] 非アルコール性脂肪性肝炎（NASH）に対するpioglitazoneの治療効果と血漿アミノ酸濃度に与える影響 (2012)
  • Author(s): 嘉数英二
  • Organizer: 第39回日本肝臓学会東部会
  • Place of Presentation: 東京
• [Presentation] Plasma L-Cystine / L-Glutamate imbalance increases tumor necrosis factor-alpha from circulating monocytes via system Xc- (4F2hc+xCT) in patients with advanced cirrhosis (2011)
  • Author(s): EIJI KAKAZU, YOSHIYUKI UENO, YASUTERU KONDO, JUN INOUE, MASASHI NINOMIYA, OSAMU KIMURA, TOORU SHIMOSEGAWA
  • Organizer: AASLD
  • Place of Presentation: San Francisico, USA
  • Year and Date: 2011-11-07
• [Presentation] 非代償性肝硬変に出現する血漿 L-Cystine/ L-Glutamate不均衡はCD14+単球内の還元型グルタチオンを低下させ炎症性サイトカインを増加させる (2011)
  • 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 木村修 岩崎隆雄 下瀬川徹
  • Organizer: JDDW
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-20
• [Presentation] 非代償性肝硬変に出現する血漿中 L-Cystine / L-Glutamate 不均衡は交換輸送体 xCT を介してCD14+単球からの炎症性サイトカイン産生を増加させる (2011)
  • 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 木村修 小原範之 涌井祐太 岩崎隆雄 下瀬川徹
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-03
• [Presentation] 非代償性肝硬変 で出現する L-Cystine/L-Glutamic acid不均衡はLPS刺激時の単球からのTNF-α産生を高め腎機能低下に関与する (2011)
  • 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: 第97回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-15
• [Presentation] 非代償性肝硬変で出現するL-Cystine / L-Glutamic acid不均衡はLPS刺激時の単球からのTNF-α産生を高め、腎機能低下に関与する
  • 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: 第９７回日本消化器病学会総会
  • Place of Presentation: 東京
• [Presentation] 非代償性肝硬変に出現する血漿中L-Cystine / L-Glutamate不均衡は交換輸送体xCTを介してCD14+単球からの炎症性サイトカイン産生を増加させる。
  • 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 木村修 小原範之 涌井祐太 岩崎隆雄 下瀬川徹
  • Organizer: 第４７回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 非代償性肝硬変に出現する血漿L-Cystine / L-Glutamate不均衡はCD14+単球内の還元型グルタチオンを低下させ炎症性サイトカインを増加させる
  • 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 木村 修 岩崎隆雄 下瀬川徹
  • Organizer: 第１９回日本消化器関連学会週間
  • Place of Presentation: 福岡
• [Presentation] Plasma L-Cystine / L-Glutamate imbalance increases tumor necrosis factor-alpha from circulating monocytes via system Xc- (4F2hc+xCT) in patients with advanced cirrhosis.
  • Author(s): EIJI KAKAZU, YOSHIYUKI UENO, YASUTERU KONDO, JUN INOUE, MASASHI NINOMIYA, OSAMU KIMURA, TOORU SHIMOSEGAWA
  • Organizer: The 62nd annual meeting of the american association for the study of liver disease (AASLD)
  • Place of Presentation: 米国 サンフランシスコ