Curiel R E, Lahesmaa R, Subleski J, Cippitelli M, Kirken R A, Young H A, Ghosh P
Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, USA.
Eur J Immunol. 1997 Aug;27(8):1982-7. doi: 10.1002/eji.1830270823.
Interleukin (IL)-4 is an immunomodulatory cytokine produced by a number of cell types including T cells, basophils, and mast cells. This pleiotropic cytokine has a number of immunoregulatory functions; however, the molecular mechanisms controlling the transcription of this gene are not yet completely understood. Several studies have implicated a possible autoregulatory mechanism for its own expression. Here, we have identified a Stat-6-responsive element (Stat-6RE) in the promoter of the human IL-4 gene. Utilizing electrophoretic mobility shift analysis, we have demonstrated the presence of two specific IL-4-responsive DNA-protein complexes in nuclear extracts of both human Th1 and Th2 clones. Phytohemagglutinin-blasted peripheral blood T cells also generated an inducible complex in response to stimulation with IL-4 and the IL-4-like cytokine IL-13. Transient transfection of the murine pre-B cell line BA/F3 stably transfected with the full-length human IL-4 receptor alpha chain demonstrated the ability of multicopy Stat-6RE to initiate transcription from a heterologous promoter upon IL-4 or IL-13 stimulation. These results indicate a possible autocrine mechanism for the regulation of IL-4 gene transcription through the Stat-6RE as well as a possible mechanism for IL-13 regulation of the human IL-4 promoter.
白细胞介素（IL）-4是一种免疫调节细胞因子，由多种细胞类型产生，包括T细胞、嗜碱性粒细胞和肥大细胞。这种多效性细胞因子具有多种免疫调节功能；然而，控制该基因转录的分子机制尚未完全清楚。几项研究表明其自身表达可能存在一种自调节机制。在此，我们在人IL-4基因启动子中鉴定出一个Stat-6反应元件（Stat-6RE）。利用电泳迁移率变动分析，我们在人Th1和Th2克隆的核提取物中均证明存在两种特异性IL-4反应性DNA-蛋白质复合物。植物血凝素刺激的外周血T细胞在受到IL-4和IL-4样细胞因子IL-13刺激时也产生了一种诱导性复合物。用全长人IL-4受体α链稳定转染的小鼠前B细胞系BA/F3进行瞬时转染，结果表明多拷贝Stat-6RE能够在IL-4或IL-13刺激下启动来自异源启动子的转录。这些结果表明通过Stat-6RE调节IL-4基因转录可能存在一种自分泌机制，以及IL-13调节人IL-4启动子的一种可能机制。
