Nuclear factor-κB in the liver of patients with chronic hepatitis C:: Decreased RelA expression is associated with enhanced fibrosis progression
Nuclear factor-κB in the liver of patients with chronic hepatitis C:: Decreased RelA expression is associated with enhanced fibrosis progression
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DOI：
10.1053/jhep.2001.29002
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发表时间：
2001-11-01
期刊：
影响因子：
13.5
通讯作者：
Prieto, J
中科院分区：
文献类型：
--
作者：
Boya, P;Larrea, E;Prieto, J
慢性丙型肝炎病毒（HCV）感染引起肝损伤的机制尚不清楚。转录因子，核因子-κ B（NF-κ B），调节参与细胞凋亡，炎症和抗病毒反应的基因的表达。它在几种形式的肝损伤中起保护作用。在这项研究中，我们分析了NF-kappaB的凝胶迁移率变动分析和免疫组化从HCV感染患者的肝活检，我们已经确定了肝水平的成分的NF-kappaB系统的半定量聚合酶链反应（PCR）。我们发现NF-κ B在慢性丙型肝炎患者的肝脏中被激活。无论是NF-κ B活性还是NF-κ B亚基的RNA水平都与肝脏炎症活动、病毒载量或HCV基因型无关。相比之下，肝脏RelA（活性NF-κ B的主要成分）的mRNA值与细胞凋亡（r = -.68; P < .05）和纤维化进展率（r = -.51; P < .04）呈负相关。在中度/快速纤维化中，RelA mRNA水平与缓慢纤维化（P <0.003）和正常肝脏（P <0.03）相比显著降低。总之，我们发现NF-κ B在慢性HCV感染的肝脏中被激活，并且RelA的表达与肝细胞凋亡和纤维化进展速率呈负相关。因此，我们的数据表明，RelA表达可能会保护肝纤维化和肝细胞损伤。
The mechanisms of liver damage in chronic hepatitis C virus (HCV) infection are poorly understood. The transcription factor, nuclear factor-kappaB (NF-kappaB), regulates the expression of genes involved in apoptosis, inflammation, and antiviral response. It plays a protective role in several forms of liver damage. In this study, we analyzed NF-kappaB by gel mobility shift assay and immunohistochemistry in liver biopsies from HCV-infected patients, and we have determined the hepatic levels of the components of the NF-kappaB system by semiquantitative polymerase chain reaction (PCR). We found that NF-kappaB was activated in the liver of patients with chronic hepatitis C. Neither NF-kappaB activity nor the RNA levels of NF-kappaB subunits showed correlation with liver inflammatory activity, viral load, or HCV genotype. By contrast, hepatic mRNA values of RelA, the main element of active NF-kappaB, correlated inversely with apoptosis (r = -.68; P < .05) and with the rate of fibrosis progression (r = -.51; P < .04). In intermediate/rapid fibrosers, RelA mRNA levels were significantly decreased as compared with slow fibrosers (P < .003) and with normal livers (P < .03). In conclusion, we found that NF-kappaB is activated in chronic HCV-infected livers, and that the expression of RelA is inversely correlated with liver cell apoptosis and with the rate of fibrosis progression. Our data thus suggest that RelA expression may protect against liver fibrosis and hepatocellular damage.