Satoh S, Nüssler A K, Liu Z Z, Thomson A W
Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15213.
Immunology. 1994 Aug;82(4):571-6.
Hepatocytes in normal tissues express low or undetectable levels of intercellular adhesion molecule-1 (ICAM-1), as detected by immunohistochemistry. Up-regulation of ICAM-1 expression on these cells has been reported in inflammatory liver disease (hepatitis B virus infection, autoimmune liver disorders and liver allograft rejection), and the molecule has been implicated in the recruitment, retention and activation of inflammatory cells. There is, however, little information concerning the regulation of hepatocyte expression of ICAM-1. We show here, for the first time, the induction (within 30 min) of ICAM-1 gene expression in cultured normal human hepatocytes stimulated with interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) or endotoxin. IFN-gamma was the most potent single inducer (up to fourfold at 6 hr), while further induction of ICAM-1 mRNA was achieved with cytokine combinations. Maximal mRNA expression was achieved within 10 hr. ICAM-1 could be detected readily by immunocytochemical staining on the hepatocyte surface by 12 hr, and by enzyme immunoassay in the culture medium by 24 hr. The data present clear evidence that cytokines, which have been implicated previously in inflammatory liver diseases, can up-regulate directly both ICAM-1 gene expression and protein secretion/shedding by human hepatocytes.
通过免疫组织化学检测发现，正常组织中的肝细胞表达低水平或无法检测到的细胞间黏附分子-1（ICAM-1）。在炎症性肝病（乙型肝炎病毒感染、自身免疫性肝病和肝移植排斥反应）中，已报道这些细胞上ICAM-1表达上调，并且该分子与炎症细胞的募集、滞留和激活有关。然而，关于肝细胞ICAM-1表达的调控信息很少。我们在此首次展示了用白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）或内毒素刺激培养的正常人肝细胞后，ICAM-1基因表达的诱导（30分钟内）。IFN-γ是最有效的单一诱导剂（6小时时高达四倍），而细胞因子组合可进一步诱导ICAM-1 mRNA。最大mRNA表达在10小时内实现。12小时时可通过免疫细胞化学染色在肝细胞表面轻松检测到ICAM-1，24小时时可通过酶免疫测定在培养基中检测到。这些数据提供了明确的证据，表明先前与炎症性肝病有关的细胞因子可直接上调人肝细胞的ICAM-1基因表达和蛋白质分泌/脱落。
