Fas / FasL system, IL-1beta expression and apoptosis in chronic HBV and HCV liver disease.
The Fas / Fas-ligand (FasL) system is an important death signal pathway in the liver. An enhanced local inflammatory response prompted by FasL expression, which contributes to neutrophil recruitment and interleukin-1 beta (IL-1beta) release, seems to be crucial to chronic liver damage, persistence of viral infections, and probably initiation and / or promotion of HCC. In order to evaluate the expression of Fas, FasL, and IL-1beta in different stages of human liver disease and to determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infections modulate their expression, also in relation to apoptosis, we examined 87 liver samples obtained from patients with: chronic hepatitis (CH) (n.42), cirrhosis (n.9) and hepatocellular carcinoma (HCC) (n.16) and corresponding peritumoural tissues (n.16); histologically-normal liver (n.4) as controls. Fas, FasL and IL-1beta mRNA were quantified using reverse transcriptase-polymerase chain reaction. The apoptotic index was evaluated by TUNEL analysis. Our data showed a progressive Fas / FasL increase from CH to cirrhosis followed by a decline from the latter to HCC. In histological sections apoptosis was detected in HCC. A significant difference emerged between HCV and HBV-related disease for IL-1beta expression only in CH. A significant positive correlation between IL-1beta and FasL in HCV-related disease (P = 0.014) and an inverse correlation between IL-1beta and Fas in HBV-related disease (P = 0.021) were observed. The different pattern of IL-1beta, Fas and FasL expression found in HCV- and HBV-mediated liver disease, points to a different modulation of immune response B and C virus induced, while the decline in Fas / FasL expression in HCC may be related to defence mechanisms adopted by HCC cells against the immune system.
Bortolami
M
M
Department of Surgical and Gastroenterological Sciences, University of Padua, Padua, Italy. marina.bortolami@unipd.it
Kotsafti
A
A
Cardin
R
R
Farinati
F
F
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000276:immunology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D053222:Fas Ligand Protein