Wang P, Wu P, Anthes J C, Siegel M I, Egan R W, Billah M M
Schering-Plough Research Institute, Kenilworth, NJ 07033.
Blood. 1994 May 1;83(9):2678-83.
In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL-6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.
在含有少于0.1%污染单核细胞的高度纯化的人多形核白细胞（PMN）制剂中，脂多糖（LPS）刺激可产生大量白细胞介素-8（IL-8）以及少量白细胞介素-1α、白细胞介素-1β和肿瘤坏死因子-α（TNF-α）。与已发表的报告相反，未检测到IL-6的产生。IL-10抑制LPS刺激的PMN中IL-1α、IL-1β、IL-8和TNF-α的产生，在富含单核细胞的人血单核细胞（MNC）制剂中也是如此。随后对IL-10对PMN细胞因子合成抑制作用的研究集中在IL-8上。IL-10以剂量依赖的方式抑制IL-8合成，在这方面，它比IL-4和转化生长因子-β1（TGF-B1）更有效。在MNC和PMN中，IL-10均增强了LPS诱导的IL-8 mRNA的降解。此外，通过核转录分析确定，IL-10抑制MNC中LPS诱导的IL-8基因转录。然而，在PMN中，转录分析无法可靠地检测到IL-8基因转录。这些结果首次证明人外周血中性粒细胞是IL-10抑制细胞因子合成的靶标，并且IL-10通过影响基因转录和mRNA稳定性发挥作用。
