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  • Review Article
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Functional role of chemokines in liver disease models

Nature Reviews Gastroenterology & Hepatology volume 7, pages 682–690 (2010)Cite this article

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Abstract

Chemokines are a class of small cytokine-like molecules that orchestrate immune cell infiltration into the liver in response to acute and chronic injuries. Apart from their chemotactic effect, however, chemokines seem to mediate many other aspects of liver diseases, including a direct activation of stellate cells, the modulation of hepatocyte proliferation and angiogenesis. The identification of specific biological functions for chemokines in liver diseases has been hampered by the finding that resident and infiltrating cells in the liver are often a source, as well as a target, of chemokines. Furthermore, chemokines might cause differing effects depending on the etiology of liver damage, their local concentrations and their ability to form multimers and heterodimers. Nevertheless, the functions of a number of important chemokines and their associated receptors have been identified in both in vivo and in vitro studies. Indeed, harmful (proinflammatory, profibrogenic) and beneficial (antifibrogenic, antiangiogenic) effects of chemokines have been discovered in experimental liver disease models. In this Review, the current knowledge of chemokines in experimental liver disease models is summarized. Advances that might lead to preclinical applications are discussed, as are the roles of chemokine receptors as promising pharmacologically targetable molecules.

Key Points

  • Chemokines are soluble mediators that are expressed by most resident and infiltrating cells in the liver following acute and chronic liver injury

  • Chemokines regulate the infiltration of immune cells and stem cells into the liver and modulate the activation and proliferation of liver-resident cells (including hepatocytes, stellate cells and endothelial cells)

  • The effects of chemokines depend on their local concentration and context within the liver as different chemokines are involved in distinct liver diseases at different disease stages

  • Antagonism of single chemokines or their receptors can ameliorate experimental acute and chronic (fibrotic) liver damage in selected models

  • Chemokines are associated with numerous human liver diseases but functional in vivo studies have not been performed in humans to date

  • Chemokine antagonists are currently under clinical investigation for use in human diseases; therefore, further elucidation and characterization of chemokine functions in liver diseases is of great clinical interest

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Figure 1: Chemokines mediate the different functions of hepatic stellate cells.
Figure 2: Immune cell infiltration and stellate cell activation mediated by chemokines in chronic liver diseases.
Figure 3: Potential therapeutic interventions to interfere with the chemokine network.

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Acknowledgements

Work on chemokines in the laboratory of H. E. Wasmuth is supported by the Deutsche Forschungsgemeinschaft (SFB TRR57 P07/P08) and Aachen University (IZKF grants).

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  1. Medical Department III, University Hospital Aachen, Pauwelsstrasse 30, D-52074, Aachen, Germany

    Hacer Sahin, Christian Trautwein & Hermann E. Wasmuth

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H. Sahin and H. E. Wasmuth contributed to researching data and writing the article. All authors provided a substantial contribution to discussions of the content and contributed to review and/or editing of the manuscript before submission.

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Correspondence to Hermann E. Wasmuth.

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Sahin, H., Trautwein, C. & Wasmuth, H. Functional role of chemokines in liver disease models. Nat Rev Gastroenterol Hepatol 7, 682–690 (2010). https://doi.org/10.1038/nrgastro.2010.168

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