Huleihel M, Douvdevani A, Segal S, Apte R N
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Eur J Immunol. 1990 Apr;20(4):731-8. doi: 10.1002/eji.1830200404.
In the present study we have demonstrated that fibroblasts can generate the inflammatory cytokine interleukin 1 (IL 1) under conditions similar to those abundant in cellular immune responses. Thus, induction of IL 1 requires a sequential two-step protocol which consists of preactivation of mouse embryo fibroblasts (MEF) with crude preparations of T cell or macrophage-derived conditioned media (CM; 72 h), followed by a challenge with lipopolysaccharide (LPS; 24 h). Unstimulated fibroblasts or such cells activated by either CM or LPS produced only low levels of IL 1, while a synergism between both signals was observed for obtaining maximal IL 1-like activity in MEF. Each of a series of individual recombinant lymphokines and cytokines (IL 2, granulocyte/macrophage-colony-stimulating factor, tumor necrosis factor, IL 1 beta and interferons-alpha, beta and gamma) was shown to serve as an efficient priming signal for the induction of IL 1. IL 1-like activity in fibroblasts was detected in cell lysates or associated with the producing-cell membrane but not in culture fluids. Immune-stimulated fibroblasts, activated under such experimental conditions, were shown to actively transcribe mRNA of both IL 1 genes (alpha and beta). For the expression of IL 1-specific mRNA in fibroblasts a single stimulus, provided by either LPS or a lymphokine/cytokine, was sufficient; however, a more intense signal was observed when both stimuli were applied. The IL 1-like biological activity of fibroblast origin was significantly reduced by anti-IL 1 alpha antibodies. Thus, fibroblasts, when activated by immune and bacterial products, generate IL 1 which in turn possibly amplifies cellular immune responses or inflammatory processes in connective tissues.
在本研究中，我们已经证明，成纤维细胞在类似于细胞免疫反应中大量存在的条件下能够产生炎性细胞因子白细胞介素1（IL-1）。因此，IL-1的诱导需要一个连续的两步方案，该方案包括用T细胞或巨噬细胞来源的条件培养基（CM；72小时）的粗制品对小鼠胚胎成纤维细胞（MEF）进行预激活，然后用脂多糖（LPS；24小时）进行刺激。未刺激的成纤维细胞或被CM或LPS激活的此类细胞仅产生低水平的IL-1，而在MEF中观察到两种信号之间存在协同作用以获得最大的IL-1样活性。一系列单独的重组淋巴因子和细胞因子（IL-2、粒细胞/巨噬细胞集落刺激因子、肿瘤坏死因子、IL-1β以及干扰素-α、β和γ）中的每一种都被证明可作为诱导IL-1的有效启动信号。在细胞裂解物中检测到成纤维细胞中的IL-1样活性，或与产生细胞膜相关，但在培养液中未检测到。在这些实验条件下被激活的免疫刺激成纤维细胞被证明可积极转录两种IL-1基因（α和β）的mRNA。对于成纤维细胞中IL-1特异性mRNA的表达，由LPS或淋巴因子/细胞因子提供的单一刺激就足够了；然而，当同时应用两种刺激时，观察到更强的信号。抗IL-1α抗体可显著降低成纤维细胞来源的IL-1样生物活性。因此，当成纤维细胞被免疫和细菌产物激活时，会产生IL-1，而IL-1反过来可能会放大细胞免疫反应或结缔组织中的炎症过程。
