title: Intrahepatic mRNA Expression of FAS, FASL, and FOXP3 Genes Is Associated with the Pathophysiology of Chronic HCV Infection.
abstract: This study aimed to evaluate the relative mRNA expression of Fas receptor (FAS), Fas ligand (FASL), and forkhead box protein 3 (FOXP3) in liver biopsy specimens obtained from patients with viral and non-viral chronic hepatitis and correlate their expression with the fibrosis stage. A total of 51 liver biopsy specimens obtained from HBV (n = 6), HCV (n = 28), and non-viral hepatic disease (NVHD) (n = 9) patients and from individuals with normal liver histology (n = 8) (control-CT) were analyzed. Quantifications of the target genes were assessed using qPCR, and liver biopsies according to the METAVIR classification. The mRNA expression levels of FAS and FASL were lower in the CT group compared to the groups of patients. The increase in the mRNA expression of FAS and FASL was correlated with higher levels of inflammation and disease progression, followed by a decline in tissues with cirrhosis, and it was also associated with increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Higher mRNA expression of FOXP3 was observed in the HCV and NVHD groups, with the peak observed among patients with cirrhosis. The increased FOXP3 mRNA expression was positively correlated with increased FAS and FASL mRNA expression and the AST and ALT levels in all patients.
  
  
  CONCLUSIONS
  These results suggest that regardless of the cause, the course of chronic liver disease may be modulated by the analyzed genes and correlated with an increase in regulatory T cells during the liver damage followed by hepatocyte destruction by Fas/FasL system and subsequent non specific lymphocytic infiltrate accumulation.
authors.affiliation: Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Ednelza da Silva Graça
authors.initials: Eda S
authors.lastname: Amoras
authors.affiliation: Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Samara Tatielle Monteiro
authors.initials: ST
authors.lastname: Gomes
authors.affiliation: Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Felipe Bonfim
authors.initials: FB
authors.lastname: Freitas
authors.affiliation: Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Bárbara Brasil
authors.initials: BB
authors.lastname: Santana
authors.affiliation: João de Barros Barreto Hospital, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Geraldo
authors.initials: G
authors.lastname: Ishak
authors.affiliation: School of Medicine, Institute of Health Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Marialva Tereza
authors.initials: MT
authors.lastname: Ferreira de Araújo
authors.affiliation: School of Medicine, Institute of Health Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Sâmia
authors.initials: S
authors.lastname: Demachki
authors.affiliation: School of Medicine, Institute of Health Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.|Hepatology Outpatient Service, Holy House of Mercy Foundation of Pará (Santa Casa de Misericórdia do Pará), Belém, Pará, Brazil.
authors.forename: Simone Regina Souza da Silva
authors.initials: SR
authors.lastname: Conde
authors.affiliation: Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Marluísa de Oliveira Guimarães
authors.initials: Mde O
authors.lastname: Ishak
authors.affiliation: Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ishak
authors.affiliation: Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará -UFPA), Belém, Pará, Brazil.
authors.forename: Antonio Carlos Rosário
authors.initials: AC
authors.lastname: Vallinoto
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism*; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D053222:Fas Ligand Protein / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000503:physiopathology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D019014:fas Receptor / Q000235:genetics*
chemical_list: C505661:FASLG protein, human; C418974:FOXP3 protein, human; D053222:Fas Ligand Protein; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D019014:fas Receptor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase