The fractalkine receptor CX3CR1 is involved in due to chronic hepatitis C infection

被引：65

作者：

Wasmuth, Hermann E. ^{[1
]}

Zaldivar, Mirko Moreno ^{[1
]}

Berres, Marie-Luise ^{[1
]}

Werth, Alexa ^{[1
]}

Scholten, David ^{[1
]}

Hillebrandt, Sonja ^{[1
,2
]}

Tacke, Frank ^{[1
]}

Schmitz, Petra ^{[1
]}

Dahl, Edgar ^{[3
]}

Wiederholt, Tonio ^{[4
]}

Hellerbrand, Claus ^{[5
]}

Berg, Thomas ^{[6
]}

Weiskirchen, Ralf ^{[7
]}

Trautwein, Christian ^{[1
]}

Lammert, Frank ^{[1
,2
]}

机构：

[1] Univ Hosp Aachen, Dept Med 3, D-52057 Aachen, Germany

[2] Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany

[3] Univ Hosp Aachen, Dept Pathol, Aachen, Germany

[4] Univ Hosp Aachen, Dept Dermatol, Aachen, Germany

[5] Univ Regensburg, Dept Med 1, D-8400 Regensburg, Germany

[6] Charite, Dept Gastroenterol & Hepatol, Berlin, Germany

[7] Univ Hosp Aachen, Inst Clin Chem & Pathobiochem, Aachen, Germany

来源：

JOURNAL OF HEPATOLOGY | 2008年 / 48卷 / 02期

关键词：

liver fibrosis; CX3CR1; fractalkine; genetic predisposition; immunology; hepatic stellate cells; hepatitis C; chemokines;

D O I：

10.1016/j.jhep.2007.09.008

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background/Aims: The chemokine receptor CX3CR1 and its specific ligand fractalkine (CX3CL1) are known to modulate inflammatory and fibroproliferative diseases. Here we investigate the role of CX3CR1/fractalkine in HCV-induced liver fibrosis. Methods: A genotype analysis of CX3CR1 variants was performed in 211 HCV-infected patients. Hepatic expression of CX3CR1 was studied in HCV-infected livers and isolated liver cell populations by RT-PCR and immunohistochemistry. The effects of fractalkine on mRNA expression of profibrogenic genes were determined in isolated hepatic stellate cells (HSC) and CX3CR1 genotypes were related to intrahepatic TIMP-1 mRNA levels. Results: The intrahepatic mRNA expression of CX3CR1 correlates with the stage of HCV-induced liver fibrosis (P = 0.03). The CX3CR1 coding variant V2491 is associated with advanced liver fibrosis, independent of the T280M variant (P = 0.009). CX3CR1 is present on primary HSC and fractalkine leads to a suppression of tissue inhibitor of metalloproteinase (TIMP)-1 mRNA in HSC (P = 0.03). Furthermore, CX3CR1 genotypes are associated with TIMP-1 mRNA expression in HCV-infected liver (P = 0.03). Conclusions: The results identify the fractalkine receptor CX3CR1 as susceptibility a gene for hepatic fibrosis in HCV infection. The modulation of TIMP-1 expression by fractalkine and CX3CR1 genotypes provides functional support for the observed genotype-phenotype association. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：208 / 215

页数：8

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