Baumann H, Morella K K, Wong G H
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263.
J Immunol. 1993 Oct 15;151(8):4248-57.
In rat hepatoma H-35 cells, TNF-alpha, like IL-1 beta, stimulates the synthesis and secretion of type 1 acute phase plasma proteins, including alpha 1-acid glycoprotein (AGP), complement component 3 (C3), hemopexin, and haptoglobin. TNF and IL-1 in combination act additively to synergistically on the expression of AGP and C3 but not on hemopexin and haptoglobin. The cytokine stimulation of AGP and C3 genes is further enhanced by hepatocyte growth factor. The effect of TNF is mediated by the type I TNF receptor as judged from the TNF-like effect elicited by the agonist antibodies to type I but not type II TNF receptor. The data suggest that, although TNF and IL-1 share considerable overlap in their signal transduction mechanism, cytokine-specific signal pathways exist that affect a subset of acute phase plasma protein genes. A potential regulatory role is attributed to the transcription factors C/EBP beta and NF-kB based on studies on transiently transfected H-35 cells.
在大鼠肝癌H - 35细胞中，肿瘤坏死因子α（TNF - α）与白细胞介素1β（IL - 1β）一样，能刺激1型急性期血浆蛋白的合成与分泌，这些蛋白包括α1 - 酸性糖蛋白（AGP）、补体成分3（C3）、血红素结合蛋白和触珠蛋白。TNF和IL - 1联合作用时，对AGP和C3的表达起相加或协同作用，但对血红素结合蛋白和触珠蛋白则无此作用。肝细胞生长因子可进一步增强细胞因子对AGP和C3基因的刺激作用。从I型TNF受体激动剂抗体引发的类似TNF的效应判断，TNF的作用是由I型TNF受体介导的，而不是II型TNF受体。数据表明，尽管TNF和IL - 1在信号转导机制上有相当大的重叠，但存在影响急性期血浆蛋白基因子集的细胞因子特异性信号通路。基于对瞬时转染H - 35细胞的研究，转录因子C/EBPβ和NF - kB被认为具有潜在的调节作用。
