Ng S B, Tan Y H, Guy G R
Institute of Molecular and Cell Biology, National University of Singapore, Republic of Singapore.
J Biol Chem. 1994 Jul 22;269(29):19021-7.
Although tumor necrosis factor (TNF) and interleukin-1 (IL) induce the expression of the IL-8, TNF-stimulated gene 6, and plasminogen activation inhibitor-2 genes and the activation of NF-kappa B with nearly identical kinetics, the two cytokines differ significantly in the induction of the IL-6 gene in all primary fibroblasts tested. IL-1 induces IL-6 gene expression after 30 min of IL-1 treatment, reaching a maximum level by 7 h, and is sustained for up to 14 h. TNF also induces the IL-6 gene expression at 30 min but the induction was low. A similar differences in the amount of IL-6 secreted was observed in the IL-1/TNF-treated cells. Measurement of IL-6 gene transcription by nuclear run-on transcription assays indicated a 4-fold higher rate of IL-6 gene transcription in IL-1-treated than in TNF-treated cells. The IL-1-induced IL-6 mRNA has a significantly longer half-life (> 6 h) compared to 30 min for TNF-treated cells. These results suggest that the induction of the IL-6 gene expression in primary human fibroblasts by TNF and IL-1 is differentially regulated at the transcriptional as well as at the post-transcriptional level.
尽管肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）能以几乎相同的动力学诱导白细胞介素-8、TNF刺激基因6和纤溶酶原激活物抑制剂-2基因的表达以及核因子-κB的激活，但在所有测试的原代成纤维细胞中，这两种细胞因子在诱导白细胞介素-6基因方面存在显著差异。白细胞介素-1在处理30分钟后诱导白细胞介素-6基因表达，7小时达到最高水平，并持续长达14小时。肿瘤坏死因子在30分钟时也诱导白细胞介素-6基因表达，但诱导水平较低。在白细胞介素-1/肿瘤坏死因子处理的细胞中，观察到分泌的白细胞介素-6量存在类似差异。通过核转录延伸试验测量白细胞介素-6基因转录表明，白细胞介素-1处理的细胞中白细胞介素-6基因转录速率比肿瘤坏死因子处理的细胞高4倍。与肿瘤坏死因子处理的细胞中30分钟的半衰期相比，白细胞介素-1诱导的白细胞介素-6 mRNA半衰期明显更长（>6小时）。这些结果表明，肿瘤坏死因子和白细胞介素-1在原代人成纤维细胞中诱导白细胞介素-6基因表达在转录和转录后水平上受到不同调节。
