Albrecht H, Schook L B, Jongeneel C V
Ludwig Institute for Cancer Research, University of Lausanne, Switzerland.
J Inflamm. 1995;45(1):64-71.
Previous work on the transcriptional regulation of the mouse TNF-alpha promoter had indicated a major role for the NF-kappa B transcription factor in the induction of the gene by endotoxin. However, similar studies using the human promoter failed to establish a role for this factor. We measured the nuclear migration of NF-kappa B and the accumulation of TNF-alpha mRNA in murine T lymphoblasts and bone marrow-derived macrophages (BMDM) under different activation conditions, seeking to establish a correlation. Activation of NF-kappa B and accumulation of TNF-alpha mRNA correlated semiquantitatively under the following conditions: (1) inhibition of NF-kappa B by dithiocarbamates; (2) induction of TNF synthesis by taxol; (3) partial induction of TNF-alpha mRNA by various inducers in macrophages from lpsd mice; and (4) inhibition of NF-kappa B activation by a protease inhibitor. However, inhibition of TNF-alpha mRNA accumulation by cAMP inducers had no effect on NF-kappa B induction. We conclude that NF-kappa B translocation is necessary, but not sufficient for the transcriptional induction of the TNF-alpha gene by LPS in macrophages or by phorbol ester and ionomycin in T lymphocytes.
先前关于小鼠肿瘤坏死因子α（TNF-α）启动子转录调控的研究表明，核因子κB（NF-κB）转录因子在内毒素诱导该基因表达过程中起主要作用。然而，使用人类启动子进行的类似研究未能证实该因子的作用。我们检测了在不同激活条件下，小鼠T淋巴母细胞和骨髓来源的巨噬细胞（BMDM）中NF-κB的核迁移以及TNF-α mRNA的积累情况，试图建立两者之间的相关性。在以下条件下，NF-κB的激活与TNF-α mRNA的积累呈半定量相关：（1）二硫代氨基甲酸盐对NF-κB的抑制作用；（2）紫杉醇对TNF合成的诱导作用；（3）脂多糖（LPS）缺陷小鼠巨噬细胞中各种诱导剂对TNF-α mRNA的部分诱导作用；（4）蛋白酶抑制剂对NF-κB激活的抑制作用。然而，环磷酸腺苷（cAMP）诱导剂对TNF-α mRNA积累的抑制作用对NF-κB的诱导没有影响。我们得出结论，在巨噬细胞中，LPS或在T淋巴细胞中佛波酯和离子霉素诱导TNF-α基因转录时，NF-κB易位是必要的，但并不足以诱导该基因转录。
