Shannon M F, Coles L S, Vadas M A, Cockerill P N
Division of Human Immunology, Hanson Centre for Cancer Research, Adelaide, South Australia.
Crit Rev Immunol. 1997;17(3-4):301-23. doi: 10.1615/critrevimmunol.v17.i3-4.30.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the many cytokines produced following T-cell activation. It is also produced in a variety of other cell types, in particular following activation by inflammatory mediators. Changes in the rate of transcription are important in the control of GM-CSF expression in T cells and in fibroblasts and endothelial cells. The GM-CSF gene contains two distinct transcriptional control regions. These are the proximal promoter consisting of the first 120 bp from the transcription start site and an enhancer located approximately 3 kb upstream from the proximal promoter. Distinct regions of the proximal promoter respond to a wide array of signals such as phorbol myristate acetate (PMA) and Ca2+ ionophore or phytohemaglutinin (PHA), CD28 activation, human T leukemia virus (HTLV)-1 tax, TNF, and interleukin 1 (IL-1). The transcription factors that mediate these responses have mainly been defined, with the major inducible proteins being the NF-kappa B/rel and AP-I families of transcription factors. In contrast to the promoter, the enhancer responds only to PMA and Ca2+ ionophore signals and binds NFAT/AP-1 complexes that appear to mediate its function.
粒细胞巨噬细胞集落刺激因子（GM-CSF）是T细胞活化后产生的多种细胞因子之一。它也在多种其他细胞类型中产生，特别是在炎症介质激活后。转录速率的变化对T细胞、成纤维细胞和内皮细胞中GM-CSF表达的控制很重要。GM-CSF基因包含两个不同的转录控制区域。一个是近端启动子，由转录起始位点上游的前120个碱基对组成，另一个是增强子，位于近端启动子上游约3 kb处。近端启动子的不同区域对多种信号作出反应，如佛波酯（PMA）和钙离子载体或植物血凝素（PHA）、CD28激活、人类T淋巴细胞白血病病毒（HTLV）-1 tax、肿瘤坏死因子（TNF）和白细胞介素1（IL-1）。介导这些反应的转录因子已基本明确，主要的诱导蛋白是NF-κB/rel和AP-1转录因子家族。与启动子不同，增强子仅对PMA和钙离子载体信号作出反应，并结合似乎介导其功能的NFAT/AP-1复合物。
