title: Mycophenolic acid induces apoptosis of hepatic stellate cells in an in vitro model of HCV.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection is an important risk factor for the development of liver fibrosis and progression to cirrhosis. Liver transplantation as terminal treatment option for liver disease requires life-long immunosuppression. However, immunomodulatory therapy may promote reinfection and renewed fibrogenesis. Immunosupressive agents may also affect the life cycle of hepatic stellate cells (HSC), the main source of extracellular matrix. We thus aimed to characterize the effects of three common immunosuppressive agents on HSC apoptosis with or without engulfment of HCV infected apoptotic bodies.
  
  
  METHODS
  LX2 cells were incubated with three different immunosuppressants (rapamycine, mycophenolic acid or cyclosporine A) and co-incubated for 24 and 48 h with apoptotic bodies (AB), produced from Huh7 cells or from Con1 cells (Huh7-cells containing a subgenomic HCV replicon). The engulfment of AB was confirmed by immunofluorescence staining. HSC viability, apoptosis rate and expression of profibrogenic and proapoptotic genes were quantified.
  
  
  RESULTS
  In LX2 cells that engulfed Con1 AB, the treatment with mycophenolic acid induced HSC apoptosis and reduced collagen 1alpha 1 expression compared to cylosporine A or rapamycine treatment. In conclusion mycophenolic acid is a potent inducer of HSC apoptosis and attenuates HSC activation and consecutively fibrogenesis in HCV infection. Translational studies will need to confirm these mono-culture results in vivo.
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Jan
authors: J
authors: Best
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Andreas
authors: A
authors: Zahn
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Anja
authors: A
authors: Beilfuß
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Svenja
authors: S
authors: Sydor
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany; Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany.
authors: Christian
authors: C
authors: Fingas
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Jan-Peter
authors: JP
authors: Sowa
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Olympia
authors: O
authors: Anastasiou
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Vito
authors: V
authors: Cicinnati
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Guido
authors: G
authors: Gerken
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Ali
authors: A
authors: Canbay
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors: Lars P
authors: LP
authors: Bechmann
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D018450:Disease Progression; D016174:Hepacivirus / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009173:Mycophenolic Acid / Q000378:metabolism*; D012367:RNA, Viral / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D012367:RNA, Viral; D009173:Mycophenolic Acid