Z Gastroenterol 2006; 44 - P230
DOI: 10.1055/s-2006-950827

Hepatitis C virus infected apoptotic cells (bodies) differentially activate hepatic Stellate cells as compared to non-infected apoptotic bodies

A Canbay 1, G Marquitan 1, L Bechmann 1, S Friedman 2, G Gerken 1, G Gores 3
  • 1Universitätsklinik Duisburg-Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany
  • 2Mt. Sinai School of Medicine; New York, Division of Liver Disease, New York, United States of America
  • 3Mayo Medical School, Clinic and Foundation, Division of Gastroenterology and Hepatology, Rochester, MN, United States of America

Aims: Infection with Hepatitis C virus (HCV) is the one of the most common infections in the world and is a common cause of chronic liver disease. Hepatocyte apoptosis, inflammation, and fibrotic reactions are key characteristics of this disease. However the potential link between HCV infection, apoptosis and stellate cell activation remains obscure. Our recent data suggest that hepatocyte apoptosis and apoptotic body engulfment plays an important role in liver injury, inflammation and fibrosis.

Based on these concepts, our AIM was to ascertain whether the engulfment of HCV infected apoptotic cells (bodies) differentially activates hepatic Stellate cells (HSC/LX-2) as compared to non-infected apoptotic bodies.

Methods: Huh7 and FCA-1 (a Huh7 derived clone containing a replicon which encodes NS5A and NS3) cells were treated with short wave UV-light (100mJ/cm2, for 5 minutes) to obtain apoptotic bodies. LX-2 cells (human stellate cell line) were incubated with infected, and non-infected apoptotic bodies, and messenger RNA transcripts for HSC activation and pro-fibrogenic markers (collagen I, TIMP-1, TGF-β1, PDGFR-β) were quantified using real-time PCR. The results are expressed as a ratio against 18S mRNA and were normalized to the values in the absence of apoptotic bodies.

Results: HSC mRNA transcript for platelet derived growth factor receptor-β, marker of HSC activation were 2.8-fold greater in HSC incubated with infected vs. non-infected apoptotic bodies. Furthermore, TGF-β1, tissue inhibitor of metalloproteinases (TIMP) and collagen α1(I) mRNA, markers of hepatic fibrogenesis, were 2,1- and 2,0- and 2,7-fold greater in LX2 cells incubated with infected apoptotic cells compared to non-infected cells.

In conclusion, our data suggest a model, whereby the engulfment of hepatocyte-derived apoptotic bodies by HSC enhances their pro-fibrogenic gene expression. These observations suggest inhibiting engulfment processes may be therapeutic in HCV induced liver fibrosis.