What is the mechanism for TLRs to modify the onset and progression of NASH?

• Project/Area Number: 21590825
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yamagata University
• Principal Investigator: TOGASHI Hitoshi 山形大学, 保健管理センター, 教授 (60192209)
• Co-Investigator(Kenkyū-buntansha): OKUMOTO Kazuo 山形大学, 医学部, 助教 (00466608)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: TLR-2 / TLR-4 / 脂肪性肝炎 / IGFBP-2 / サイトカイン / ノックアウトマウス / NASH / NAFLD / メチオニン・コリン欠乏食 / TLR2 / TLR4 / 免疫組織化学 / 腹部超音波 / in situ hybridization / サイトカイン抗体アレイ / kupffer細胞 / ヒト

Research Abstract

We investigated the role of TLR-2 and TLR-4 in the onset and progression of nonalcoholic steatohepatitis. Wild type, TLR-2(-/-), and TLR-4(-/-) mice were used and experimental steatohepatitis was induced. TLR-2(-/-) group exacerbated the steatohepatitis and TLR-4(-/-) group completely attenuated it. TLR-2(-/-) group decreased the expression of IGFBP-2 and increased the expression of pro-inflammatory cytokines in the liver. Opposite results were observed in TLR-4(-/-) group. Here we showed that TLR-2 attenuated steatohepatitis and TLR-4 exacerbated it by differential expression of various kinds of cytokines.

Research Products

• [Journal Article] Potential therapeutic application of intravenous bone marrow in fusion in patients with alcoholic liver cirrhosis (2011)
  • Author(s): Saito T, Okumoto K, et al.
  • Journal Title: Stem Cells Dev Volume: 20 Issue: 7 Pages: 1503-1510
  • DOI: 10.1007/s12149-011-0484-0
  • Peer Reviewed
• [Journal Article] Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis (2011)
  • Author(s): Saito T, Okumoto K, Togashi H (14名中10番目), et al
  • Journal Title: Stem Cells Dev Volume: 20 Issue: 9 Pages: 1503-1509
  • DOI: 10.1089/scd.2011.0074
  • Peer Reviewed
• [Journal Article] Enhance expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocytes lineage (2011)
  • Author(s): Haga H, Okumoto K, Togashi H (12名中11番目), et al
  • Journal Title: Cell Tissue Res Volume: 343 Issue: 2 Pages: 371-378
  • DOI: 10.1007/s00441-010-1093-2
  • Peer Reviewed
• [Journal Article] A case of monocular blindness as the initial presentation of hepatocellular carcinoma with skull metastasis (2011)
  • Author(s): Ito J, Okumoto K, Togashi H (15名中14番目), et al
  • Journal Title: Clin J Gstroenterol Volume: 4 Issue: 4 Pages: 273-277
  • DOI: 10.1007/s12328-011-0237-6
  • Peer Reviewed
• [Journal Article] Time for liver injury and repair (2010)
  • Author(s): Togashi H
  • Journal Title: Hepatol Res Volume: 40 Pages: 1060-1062
  • Peer Reviewed
• [Journal Article] Expression of RNA-binding protein Musashi1 in adult liver stem-cells (2010)
  • Author(s): Hattori E, Okumoto K, Togashi H (11名中10番目), et al
  • Journal Title: Hepatol Res Volume: 40 Pages: 432-437
  • Peer Reviewed
• [Journal Article] Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C (2010)
  • Author(s): Sanjo M, Saito T, Ishii R, Nishise Y, Haga H, Okumoto K, Ito J, Watanabe H, Saito K, Togashi H, Fukuda K, Imai Y, El-Shamy A, Deng L, Shoji I, Hotta H, Kawata S
  • Journal Title: J Med Virol Volume: 82 Issue: 8 Pages: 1364-1370
  • DOI: 10.1002/jmv.21818
  • Peer Reviewed
• [Journal Article] Relationship between alcohol consumption and serum adiponectin levels: the Takahata study-a cross-sectional study of a healthy Japanese population (2010)
  • Author(s): Nishise Y, Saito T, Makino N, et al.
  • Journal Title: J Clin EndocrinolMetab Volume: 95 Issue: 8 Pages: 3828-3835
  • DOI: 10.1210/jc.2009-1862
  • Peer Reviewed
• [Journal Article] Relationship between alcohol consumption and serum adiponectin levels : the Takahata study--a cross-sectional study of a healthy Japanese population (2010)
  • Author(s): Nishise Y, Togashi H, et al
  • Journal Title: J Clin Endocrinol Metab Volume: 95 Pages: 3828-3835
  • Peer Reviewed
• [Journal Article] Association study between the-1021C/T polymorphism of the dopamine-beta-hydroxylase gene promoter and personality traits in healthy subjects (2009)
  • Author(s): Kamata M, Togashi H (7名中5番目), et al
  • Journal Title: Neurosci Lett Volume: 462 Issue: 1 Pages: 54-57
  • DOI: 10.1016/j.neulet.2009.06.077
  • Peer Reviewed
• [Journal Article] Impact of metabolic syndrome on elevated serum alanine aminotransferase levels in theJapanese population (2009)
  • Author(s): Saito T, Nishise Y, Makino N, et al.
  • Journal Title: Metabolism Volume: 58 Issue: 8 Pages: 1067-1075
  • DOI: 10.1016/j.metabol.2009.03.008
  • Peer Reviewed
• [Journal Article] Association study between the -1021C/T polymorphism of the dopamine-beta-hydroxylase gene promoter and personality traits in healthy subjects. (2009)
  • Author(s): Kamata M, Togashi H, Otani K, et al.
  • Journal Title: Neurosci Lett. 462 Pages: 54-57
  • Peer Reviewed
• [Journal Article] Impact of metabolic syndrome on elevated serum alanine aminotransferase levels in the Japanese population. (2009)
  • Author(s): Saito T, Togashi H, Kawata S, et al.
  • Journal Title: Metabolism 58 Pages: 1067-1075
  • Peer Reviewed
• [Journal Article] 大学生における食育について-特にBMI高値学生に対して- (2009)
  • Author(s): 早坂真貴子、冨樫整, 他
  • Journal Title: CAMPUS HEALTH 46(1) Pages: 170-172
• [Journal Article] (2009)
  • Author(s): 冨樫整、河田純男
  • Journal Title: 改訂第7版内科学書:糖原病、尿素代謝異常、肝アミロイドーシス、肝脂質蓄積症、肝性ポルフィリン症、α1アンチトリプシン欠乏症、色素代謝異常(小川聡:総編集、井廻道夫:部門編集)(中山書店) Pages: 275-280
• [Presentation] 過体重・肥満新入生における生活習慣病危険因子の横断的研究 (2010)
  • Author(s): 早坂真貴子, 冨樫整, 他
  • Organizer: 第48回全国大学保健管理研究集会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 2010-10-21
• [Presentation] 過体重・肥満新入生における生活習慣病危険因子の横断的研究 (2010)
  • Author(s): 早坂真貴子、冨樫整, 他
  • Organizer: 第48回全国大学保健管理研究集会
  • Place of Presentation: 千葉市(幕張メッセ)
  • Year and Date: 2010-10-21
• [Presentation] 肥満学生における各種検査成績と食習慣の分析 (2009)
  • Author(s): 早坂真貴子, 冨樫整, 他
  • Organizer: 第47回全国大会保健管理研究集会
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2009-09-17
• [Presentation] 肥満学生における各種検査成績と食習慣の分析 (2009)
  • Author(s): 早坂真貴子、冨樫整, 他
  • Organizer: 第47回全国大会保健管理研究集会
  • Place of Presentation: 札幌市
  • Year and Date: 2009-09-17
• [Book] 改訂第7版内科学書(中山書店)、糖原病、尿素代謝異常、肝アミロイドーシス、肝脂質蓄積症、肝性ポルフィリン症、α1アンチトリプシン欠乏症、色素代謝異常 (2009)
  • Author(s): 冨樫整, 河田純男
  • Publisher: 中山書店