Ayres R C, Neuberger J M, Shaw J, Joplin R, Adams D H
Liver Unit, Queen Elizabeth Hospital, Birmingham.
Gut. 1993 Sep;34(9):1245-9. doi: 10.1136/gut.34.9.1245.
Human intrahepatic biliary epithelial cells were isolated from the livers of patients with primary biliary cirrhosis and from normal livers and established in primary culture. The in vitro expression of intercellular adhesion molecule-1, HLA class I, and HLA class II on biliary epithelial cells was studied in response to tumour necrosis factor-alpha (0-500 U/ml), interferon-gamma (0-500 U/ml), and interleukin-1 (0-5 U/ml) by immunohistochemical staining and a semiquantitative scoring system validated by spectrophotometry and previously validated by laser confocal microscopy. The non-stimulated expression of intercellular adhesion molecule-1 and HLA class II was higher on cells derived from the primary biliary cirrhosis liver than on cells from normal liver, a difference not seen with HLA class I expression. A statistically significant increase in intercellular adhesion molecule-1 expression was seen with all three cytokines in cells derived from both primary biliary cirrhosis and normal liver. Increase in HLA class I expression was seen only with interleukin-1 5 U/ml for cells derived from both normal and diseased liver. Increase in HLA class II expression was seen only with interferon-gamma 500 U/ml for cells derived from diseased liver and with interleukin-1 5 U/ml for cells derived from both diseased and normal liver. These data show that pro-inflammatory cytokines increase expression of intercellular adhesion molecule-1, HLA class I, and HLA class II on human intrahepatic biliary epithelial cells in vitro and are consistent with the hypothesis that these locally acting factors may play a part in the pathogenesis of immune mediated disorders such as primary biliary cirrhosis in which immune mediated bile duct damage occurs.
从原发性胆汁性肝硬化患者的肝脏和正常肝脏中分离出人肝内胆管上皮细胞，并进行原代培养。通过免疫组织化学染色和经分光光度法验证且先前已通过激光共聚焦显微镜验证的半定量评分系统，研究了肿瘤坏死因子-α（0 - 500 U/ml）、干扰素-γ（0 - 500 U/ml）和白细胞介素-1（0 - 5 U/ml）作用下胆管上皮细胞上细胞间黏附分子-1、HLAⅠ类和HLAⅡ类分子的体外表达情况。原发性胆汁性肝硬化肝脏来源的细胞上细胞间黏附分子-1和HLAⅡ类分子的非刺激表达高于正常肝脏来源的细胞，而HLAⅠ类分子表达未见此差异。原发性胆汁性肝硬化和正常肝脏来源的细胞在所有三种细胞因子作用下，细胞间黏附分子-1表达均有统计学意义的增加。正常和患病肝脏来源的细胞仅在白细胞介素-1 5 U/ml作用下HLAⅠ类分子表达增加。患病肝脏来源的细胞仅在干扰素-γ 500 U/ml作用下HLAⅡ类分子表达增加，而患病和正常肝脏来源的细胞在白细胞介素-1 5 U/ml作用下HLAⅡ类分子表达均增加。这些数据表明，促炎细胞因子可增加人肝内胆管上皮细胞上细胞间黏附分子-1、HLAⅠ类和HLAⅡ类分子的表达，这与这些局部作用因子可能参与免疫介导疾病（如发生免疫介导胆管损伤的原发性胆汁性肝硬化）发病机制的假说一致。
