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

Hermann E. Wasmuth; Mirko Moreno Zaldivar; Marie Luise Berres; Alexa Werth; David Scholten; Sonja Hillebrandt; Frank Tacke; Petra Schmitz; Edgar Dahl; Tonio Wiederholt; Claus Hellerbrand; Thomas Berg; Ralf Weiskirchen; Christian Trautwein; Frank Lammert

doi:10.1016/j.jhep.2007.09.008

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

Hermann E. Wasmuth, Mirko Moreno Zaldivar, Marie Luise Berres, Alexa Werth, David Scholten, Sonja Hillebrandt, Frank Tacke, Petra Schmitz, Edgar Dahl, Tonio Wiederholt, Claus Hellerbrand, Thomas Berg, Ralf Weiskirchen, Christian Trautwein, Frank Lammert

Research output: Contribution to journal › Article › peer-review

69 Scopus citations

Abstract

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 V249I 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.

Original language	English
Pages (from-to)	208-215
Number of pages	8
Journal	Journal of Hepatology
Volume	48
Issue number	2
DOIs	https://doi.org/10.1016/j.jhep.2007.09.008
State	Published - Feb 2008
Externally published	Yes

Keywords

CX3CR1
Chemokines
Fractalkine
Genetic predisposition
Hepatic stellate cells
Hepatitis C
Immunology
Liver fibrosis

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10.1016/j.jhep.2007.09.008

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Wasmuth, H. E., Zaldivar, M. M., Berres, M. L., Werth, A., Scholten, D., Hillebrandt, S., Tacke, F., Schmitz, P., Dahl, E., Wiederholt, T., Hellerbrand, C., Berg, T., Weiskirchen, R., Trautwein, C., & Lammert, F. (2008). The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection. Journal of Hepatology, 48(2), 208-215. https://doi.org/10.1016/j.jhep.2007.09.008

@article{ae65fde185124f0095f9ed4144050cad,

title = "The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection",

abstract = "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 V249I 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.",

keywords = "CX3CR1, Chemokines, Fractalkine, Genetic predisposition, Hepatic stellate cells, Hepatitis C, Immunology, Liver fibrosis",

author = "Wasmuth, \{Hermann E.\} and Zaldivar, \{Mirko Moreno\} and Berres, \{Marie Luise\} and Alexa Werth and David Scholten and Sonja Hillebrandt and Frank Tacke and Petra Schmitz and Edgar Dahl and Tonio Wiederholt and Claus Hellerbrand and Thomas Berg and Ralf Weiskirchen and Christian Trautwein and Frank Lammert",

note = "Funding Information: The study was supported by grants from the Deutsche Forschungsgemeinschaft to H.E.W. (WA 2557/1-1) and F.L.; the German Network of Excellence for Viral Hepatitis (Kompetenznetz Hepatitis Hep-Net) to H.E.W., C.T. and F.L.; the Ministry of Science and Research of North-Rhine Westphalia (to F.L.); the Federal Ministry of Education and Research (to F.L.), Aachen University (START grant to H.E.W., F.T. and T.W.); and a grant from the Interdisciplinary Centre for Clinical Research “BIOMAT.” at Aachen University (to H.E.W.). ",

year = "2008",

month = feb,

doi = "10.1016/j.jhep.2007.09.008",

language = "English",

volume = "48",

pages = "208--215",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier B.V.",

number = "2",

}

Wasmuth, HE, Zaldivar, MM, Berres, ML, Werth, A, Scholten, D, Hillebrandt, S, Tacke, F, Schmitz, P, Dahl, E, Wiederholt, T, Hellerbrand, C, Berg, T, Weiskirchen, R, Trautwein, C & Lammert, F 2008, 'The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection', Journal of Hepatology, vol. 48, no. 2, pp. 208-215. https://doi.org/10.1016/j.jhep.2007.09.008

TY - JOUR

T1 - The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection

AU - Wasmuth, Hermann E.

AU - Zaldivar, Mirko Moreno

AU - Berres, Marie Luise

AU - Werth, Alexa

AU - Scholten, David

AU - Hillebrandt, Sonja

AU - Tacke, Frank

AU - Schmitz, Petra

AU - Dahl, Edgar

AU - Wiederholt, Tonio

AU - Hellerbrand, Claus

AU - Berg, Thomas

AU - Weiskirchen, Ralf

AU - Trautwein, Christian

AU - Lammert, Frank

N1 - Funding Information: The study was supported by grants from the Deutsche Forschungsgemeinschaft to H.E.W. (WA 2557/1-1) and F.L.; the German Network of Excellence for Viral Hepatitis (Kompetenznetz Hepatitis Hep-Net) to H.E.W., C.T. and F.L.; the Ministry of Science and Research of North-Rhine Westphalia (to F.L.); the Federal Ministry of Education and Research (to F.L.), Aachen University (START grant to H.E.W., F.T. and T.W.); and a grant from the Interdisciplinary Centre for Clinical Research “BIOMAT.” at Aachen University (to H.E.W.).

PY - 2008/2

Y1 - 2008/2

N2 - 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 V249I 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.

AB - 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 V249I 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.

KW - CX3CR1

KW - Chemokines

KW - Fractalkine

KW - Genetic predisposition

KW - Hepatic stellate cells

KW - Hepatitis C

KW - Immunology

KW - Liver fibrosis

UR - https://www.scopus.com/pages/publications/37848999947

U2 - 10.1016/j.jhep.2007.09.008

DO - 10.1016/j.jhep.2007.09.008

M3 - Article

C2 - 18078680

AN - SCOPUS:37848999947

SN - 0168-8278

VL - 48

SP - 208

EP - 215

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 2

ER -

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

Abstract

Keywords

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