Bosco M C, Gusella G L, Espinoza-Delgado I, Longo D L, Varesio L
Laboratory of Experimental Immunology, BRMP, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
Blood. 1994 Jan 15;83(2):537-42.
Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time-dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL-8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.
白细胞介素-8（IL-8）是一种中性粒细胞趋化性和激活细胞因子，可响应多种刺激而产生。由于单核细胞是IL-8的重要产生者，我们研究了γ干扰素（IFN-γ）这种单核吞噬细胞激活和分化的强效诱导剂是否会影响该细胞系中IL-8的表达。我们发现，在人单核细胞系U937中，IL-8 mRNA表达存在低水平的组成性表达，其可被IFN-γ以剂量和时间依赖性方式以及通过蛋白质合成依赖性过程上调。IFN-γ也刺激了IL-8蛋白的分泌。细胞核连续标记实验表明，IL-8基因在对照细胞中具有转录活性，而IFN-γ并未增强其转录活性。IFN-γ导致IL-8 mRNA增加的同时伴随着mRNA的稳定，因此主要在转录后水平受到调控。这些结果首次证明IFN-γ上调单核细胞系细胞中IL-8基因的表达，并表明转录后机制参与了IL-8 mRNA的诱导过程。
