title: The pro-fibrotic effects of pregnancy in a carbon-tetrachloride-induced liver injury in mouse model.
abstract: OBJECTIVE
  Immune cells interact with hepatic-stellate-cells (HSCs) in the development of liver fibrosis. Little is known about the influence of pregnancy on the development and progression of hepatic-fibrosis. In this study, we explored the influence of pregnancy on progression of hepatic fibrosis.
  
  
  METHODS
  Female mice (C57Blc) were induced by 4 injections of peritoneal carbon-tetrachloride (CCl4) within 10 days, starting at day 10 of documented pregnancy. At end of experiment, serum samples were obtained for ALT and estradiol determination. Harvested livers were histological evaluated for liver injury and for protein αSMA expressions. Isolated intra-hepatic lymphocytes were assessed by flow cytometry. Isolated lymphocytes and serum samples were in- vitro co-cultured for 48 h with primary isolated naïve HSCs. Washed cells were analyzed for adherence (anti-αSMA+/anti-CD45 + ) and proliferations (CSFE).
  
  
  RESULTS
  CCl4-model for liver injury was well tolerated when induced in pregnancy similar to non-pregnant state. Hepatic-fibrosis (Masson Trichrome Stain, Sirius red stain and αSMA expressions) and necro-inflammation (H&E stain and serum ALT levels) significantly increased in pregnancy. Increased liver injury was accompanied with pro-fibrotic lymphocyte profile; CD8 subsets increased and NK cells decreased. HSCs activation significantly increased when in-vitro cultured with lymphocytes from pregnant as compared to non-pregnant fibrotic ones. Pro-fibrotic profile was also explained by decreased NK activity (CD107a marker) and of their phagocytosis. Serum estradiol levels although elevated in fibrosis conditions of pregnancy was not associated with the pHSCs activations.
  
  
  CONCLUSIONS
  Liver fibrosis in our murine model was severe in pregnant model; via pro-fibrotic lymphocyte and serum alterations.
authors: The Liver and Gastroenterology Units, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Johnny
authors: J
authors: Amer
authors: Rami
authors: R
authors: Grifat
authors: Sarit
authors: S
authors: Doron
authors: Lina
authors: L
authors: Abu-Tair
authors: Rufayda
authors: R
authors: Mruwat
authors: Areej
authors: A
authors: El-Khatib
authors: Rifaat
authors: R
authors: Safadi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004958:Estradiol / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D007694:Killer Cells, Natural / Q000276:immunology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D052118:Lysosomal-Associated Membrane Protein 1; D004958:Estradiol; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase
keywords: NK cells; immune modulation; liver disease; pregnancy