Oliveira I C, Sciavolino P J, Lee T H, Vilcek J
Department of Microbiology, New York University Medical Center, New York 10016.
Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9049-53. doi: 10.1073/pnas.89.19.9049.
The chemotactic cytokine interleukin 8 (IL-8) is produced upon stimulation by various agents in many cell types, including connective-tissue fibroblasts. Tumor necrosis factor (TNF) and IL-1 are potent inducers of IL-8 expression. Earlier we showed that TNF-induced stimulation of IL-8 mRNA accumulation in human FS-4 fibroblasts was inhibited by interferon beta (IFN-beta) or IFN-gamma. Here we show that this inhibition is not specific for TNF, since IFN-beta also reduced IL-8 mRNA accumulation induced by IL-1 or the double-stranded RNA poly (I-C). Treatment with IFN-beta also decreased TNF-induced IL-8 protein accumulation. Interestingly, the inhibitory effect was much less pronounced when IFN-beta was added greater than or equal to 1 hr before TNF. The inhibitory action of IFN-beta on IL-8 mRNA accumulation was undiminished in the presence of inhibitors of protein synthesis. Nuclear run-on assays demonstrated that IFN-beta caused a marked inhibition of TNF-induced IL-8 gene transcription; the transcriptional activation of several other TNF-induced genes was not inhibited by IFN-beta. The results suggest that the specific inhibition of the transcriptional activation of IL-8 by IFN is due either to a transient inactivation of a factor required for IL-8 transcription or to the activation of a selective inhibitory factor.
趋化细胞因子白细胞介素8（IL-8）在包括结缔组织成纤维细胞在内的多种细胞类型中，受多种因子刺激后产生。肿瘤坏死因子（TNF）和白细胞介素1（IL-1）是IL-8表达的强效诱导剂。此前我们发现，干扰素β（IFN-β）或干扰素γ（IFN-γ）可抑制TNF诱导的人FS-4成纤维细胞中IL-8 mRNA的积累。在此我们表明，这种抑制作用并非TNF所特有，因为IFN-β也能降低IL-1或双链RNA聚肌胞苷酸（poly (I-C)）诱导的IL-8 mRNA积累。用IFN-β处理也能减少TNF诱导的IL-8蛋白积累。有趣的是，当IFN-β在TNF之前1小时或更长时间添加时，其抑制作用明显减弱。在存在蛋白质合成抑制剂的情况下，IFN-β对IL-8 mRNA积累的抑制作用并未减弱。核转录分析表明，IFN-β可显著抑制TNF诱导的IL-8基因转录；IFN-β并未抑制其他几种TNF诱导基因的转录激活。结果表明，IFN对IL-8转录激活的特异性抑制，要么是由于IL-8转录所需因子的短暂失活，要么是由于选择性抑制因子的激活。
