Gut-liver axis mediated by endotoxin and innate immunity
Project/Area Number |
23590987
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Nara Medical University |
Principal Investigator |
FUKUI HIROSHI 奈良県立医科大学, 医学部, 教授 (80145838)
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Co-Investigator(Renkei-kenkyūsha) |
YOSHIJI Hitoshi 奈良県立医科大学, 医学科, 准教授 (40336855)
FUJIMOTO Masao 奈良県立医科大学, 医学科, 講師 (60295805)
NAMISAKI Tadashi 奈良県立医科大学, 医学科, 助教 (20526850)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | エンドトキシン / 自然免疫 / Toll-like受容体 / 非アルコール性脂肪肝炎 / 腸管相関 / 難吸収性抗菌薬 / ウルソデオキシコール酸 / 急性肝不全 / TNF-α |
Research Abstract |
The underling cause of nonalcoholic steatohepatitis is still unlear, but intestinal bacterial flora and endotoxin are important factors. We evaluated pathogenic roles of endotoxin, intestinal permeability and innate immunity on the development of liver fibrosis in rats fed choline-deficient and amino acid-defined (CDAA) diet. In these rats, marked fibrosis was associated with increased intestinal permeability, augmented development of Toll-like recrptor 4 (TLR4) mRNA, lipopolysaccharide binding protein (LBP) mRNA and TNF-alpha mRNA in the liver. Oral administrations of nonabsorbable antibiotics for selective bowel decontamination and ursodeoxycholic acids were demonstrated to suppress intestinal permeability and TLR4 mediated inflammation and finally inhibit progression of fibrosis. Regulation of gut-liver axis may become a new strategy for prevention of human steatohepatitis.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] The effect of inflammatory cytokines in alcoholic liver disease. Mediators2013
Author(s)
Kawaratani, H. Tsujimoto, T. Douhara, A. Takaya, H. Moriya, K. Namisaki, T. Noguchi, R. Yoshiji, H. Fujimoto, M. Fukui, H.
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Journal Title
Mediators Inflamm
Volume: 2013
Pages: 495156-495156
DOI
Related Report
Peer Reviewed
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[Journal Article] 急性肝不全における血漿エンドトキシン濃度とADAMTS13活性の動態 新規治療法の可能性を含めて2013
Author(s)
高谷 広章, 植村 正人, 藤本 正男, 松山 友美, 森岡 千恵, 石川 昌利, 辻本 達寛, 瓦谷 英人, 北澤 利幸, 早川 正樹, 松本 雅則, 藤村 吉博, 福井 博
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Journal Title
エンドトキシン・自然免疫研究
Volume: 16
Pages: 16-20
Related Report
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[Journal Article] ADAMTS13 activity may predict the cumulative survival of patients with liver cirrhosis in comparison with the Child-Turcotte-Pugh score and the Model for End-Stage Liver Disease score2012
Author(s)
Takaya H, Uemura M, Fujimura Y, Matsumoto M, Matsuyama T, Kato S, Morioka C, Ishizashi H, Hori Y, Fujimoto M, Tsujimoto T, Kawaratani H, Toyohara M, Kurumatani N, Fukui H.
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Journal Title
Hepatol Res.
Volume: 42
Pages: 459-72
NAID
Related Report
Peer Reviewed
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[Book] 急性肝不全における血漿エンドトキシン濃度とADAMTS13活性の動態新規治療法の可能性を含めて2013
Author(s)
高谷広章,植村正人,藤本正男,松山友美,森岡千恵,石川昌利,辻本達寛,瓦谷英人,北澤利幸,早川正樹,松本雅則,藤村吉博,福井博
Publisher
エンドトキシン・自然免疫研究
Related Report
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[Book] 肝不全における血漿エンドトキシン濃度とADAMTS13活性の動態2011
Author(s)
高谷広章,植村正人,藤本正男,松山友美,森岡千恵,石川昌利,辻本達寛,瓦谷英人,松本雅則,藤村吉博,福井博
Publisher
エンドトキシン・自然免疫研究
Related Report
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