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

2012 Fiscal Year Final Research Report

• 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
• 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

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 of hepatitis C virus could improve immunological status and pyoderma gangrenosum-like lesions (2013)
  • Author(s): Kondo, Y., Iwata, T., Haga, T., Kimura, O., Ninomiya, M., Kakazu, E., Kogure, T., Morosawa, T., Aiba, S., and Shimosegawa, T.
  • Journal Title: Hepatology research : the official journal of the Japan Society of Hepatology
  • DOI: 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): Kondo, Y., Ninomiya, M., Kakazu, E., Kimura, O., and Shimosegawa, T.
  • Journal Title: ISRN gastroenterology Pages: 935295
  • DOI: doi:10.1155/2013/935295.
  • Peer Reviewed
• [Journal Article] The Relationship between Renal Dysfunction and Abnormalities of the Immune System in Patients with Decompensated Cirrhosis (2012)
  • Author(s): Kakazu, E., Kondo, Y., and Shimosegawa, T.
  • Journal Title: ISRN gastroenterology Pages: 123826
  • DOI: 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): Inoue, J., Ueno, Y., Kawamura, K.,Yamamoto, T., Mano, Y., Miura, M., Kobayashi, T., Niitsuma, H., Kondo, Y., Kakazu, E., Ninomiya, M., Kimura, O., Obara, N., Kawagishi, N., Kinouchi, Y., and Shimosegawa, T.
  • Journal Title: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Volume: 55 Pages: 147-152
  • DOI: doi:10.1016/j.jcv.2012.06.011.
  • Peer Reviewed
• [Journal Article] Use of illumina deep sequencing technology to differentiate hepatitis C virus variants (2012)
  • Author(s): Ninomiya, M., Ueno, Y., Funayama, R., Nagashima, T., Nishida, Y., Kondo, Y., Inoue, J., Kakazu, E., Kimura, O., Nakayama, K., and Shimosegawa, T
  • Journal Title: Journal of clinical microbiology Volume: 50 Pages: 857-866
  • DOI: 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., and Sugamura, K.
  • Journal Title: Virology Volume: 422 Pages: 377-385
  • DOI: doi:10.1016/j.virol.2011.11.009.
  • Peer Reviewed
• [Journal Article] Sequential immunologicalanalysis of HBV/HCV co-infected patients during Peg-IFN/RBV therapy (2012)
  • Author(s): Kondo, Y., Ueno, Y., Ninomiya, M., Tamai, K., Tanaka, Y., Inoue, J., Kakazu, E., Kobayashi, K., Kimura, O., Miura, M., Yamamoto, T., Kobayashi, T., Igarashi, T., and Shimosegawa, T.
  • Journal Title: Journal of gastroenterology Volume: 47 Pages: 1323-1335
  • DOI: 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 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 Pages: 215-219
  • DOI: doi:10.1620/tjem.224.215.
  • 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 Pages: 1017-1025
  • DOI: doi:10.1093/infdis/jir485.
  • Peer Reviewed
• [Journal Article] PlasmaL-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., and Shimosegawa, T.
  • Journal Title: PloS one Volume: 6 Pages: e23402
  • DOI: doi:10.1371/journal.pone.0023402.
  • Peer Reviewed
• [Journal Article] Rapid reduction of hepatitis C virus-Core protein in the peripheral blood improve the immunological response in chronic hepatitis C patients (2011)
  • Author(s): Kondo, Y., Ueno, Y., Wakui, Y., Ninomiya, M., Kakazu, E., Inoue, J., Kobayashi, K., Obara, N., and Shimosegawa, T.
  • Journal Title: Hepatology research : the official journal of the Japan Society of Hepatology Volume: 41 Pages: 1153-1168
  • DOI: doi:10.1111/j.1872-034X.2011.00878.x.
  • Peer Reviewed
• [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