Fas/FasL system, IL-1β expression and apoptosis in chronic HBV and HCV liver disease
Fas/FasL system, IL-1β expression and apoptosis in chronic HBV and HCV liver disease
复制标题
DOI：
10.1111/j.1365-2893.2008.00974.x
复制
发表时间：
2008-07-01
影响因子：
2.5
通讯作者：
Farinati, F.
中科院分区：
文献类型：
--
作者：
Bortolami, M.;Kotsafti, A.;Farinati, F.
Fas/Fas配体（FasL）系统是肝脏中重要的死亡信号通路。FasL表达引起的局部炎症反应增强，有助于中性粒细胞募集和白细胞介素-1 β (IL-1 β)释放，似乎对慢性肝损伤、病毒感染的持续存在以及HCC的发生和/或促进至关重要。为了评估Fas、FasL和IL-1 β在人类肝脏疾病不同阶段的表达，并确定乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染是否会调节它们的表达，以及它们与细胞凋亡的关系，我们检测了87例来自慢性肝炎（CH） （n.42）、肝硬化（n.9）和肝细胞癌（n.16）及相应肿瘤周围组织（n.16）患者的肝脏样本；组织学正常的肝脏（n.4）作为对照。采用逆转录-聚合酶链反应定量Fas、FasL和IL-1 β mRNA。TUNEL法测定细胞凋亡指数。我们的数据显示，从肝纤维化到肝硬化，Fas/FasL呈进行性增加，随后从肝硬化到HCC呈下降趋势。肝细胞癌组织切片检测到细胞凋亡。IL-1 β仅在CH中的表达在HCV与hbv相关疾病中存在显著差异。在HCV相关疾病中，IL-1 β与FasL呈显著正相关（P = 0.014），在hbv相关疾病中，IL-1 β与Fas呈显著负相关（P = 0.021）。在HCV和hbv介导的肝脏疾病中发现IL-1 β、Fas和FasL表达的不同模式，表明B和C病毒诱导的免疫反应的不同调节，而HCC中Fas/FasL表达的下降可能与HCC细胞对免疫系统采取的防御机制有关。
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-1 beta) 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-1 beta 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-1 beta 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-1 beta expression only in CH. A significant positive correlation between IL-1 beta and FasL in HCV-related disease (P = 0.014) and an inverse correlation between IL-1 beta and Fas in HBV-related disease (P = 0.021) were observed. The different pattern of IL-1 beta, 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.