Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation

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Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation

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Title: Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation
Author: Bility, Moses T.; Nio, Kouki; Li, Feng; McGivern, David R.; Lemon, Stanley M.; Feeney, Eoin R.; Chung, Raymond T.; Su, Lishan

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Citation: Bility, Moses T., Kouki Nio, Feng Li, David R. McGivern, Stanley M. Lemon, Eoin R. Feeney, Raymond T. Chung, and Lishan Su. 2016. “Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation.” Scientific Reports 6 (1): 39520. doi:10.1038/srep39520. http://dx.doi.org/10.1038/srep39520.
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Abstract: The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV–induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV–induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis.
Published Version: doi:10.1038/srep39520
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175173/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29738991
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