Mitchell R, Bacher M, Bernhagen J, Pushkarskaya T, Seldin M F, Bucala R
Picower Institute for Medical Research, Manhasset, NY 11030, USA.
J Immunol. 1995 Apr 15;154(8):3863-70.
An emerging body of data indicates that the protein mediator described originally as macrophage migration inhibitory factor (MIF) exerts a central and wide ranging role in host inflammatory responses. MIF is a major constituent of corticotrophic cells within the anterior pituitary gland and is secreted into the circulation in a hormone-like fashion. MIF also exists performed in monocytes/macrophages and is a pivotal mediator in the host response to endotoxic shock. To gain further insight into the biologic expression of this protein that encompasses components of both the immune and the endocrine systems, we have cloned the mouse MIF gene and identified potential regulatory sequences present within the 5'-proximal promoter region. The gene for mouse MIF is located on chromosome 10, spans approximately 1 kb, and shares a high degree of structural homology with its human counterpart. Of note, the consensus enhancer/promoter motifs identified include both inflammatory/growth factor-related elements and sites associated with the genes for certain peptide hormones. We also report the structures of two MIF pseudogenes that account for early observations suggesting that mouse MIF is encoded by a highly homologous multigene family.
越来越多的数据表明,最初被描述为巨噬细胞移动抑制因子(MIF)的蛋白质介质在宿主炎症反应中发挥着核心且广泛的作用。MIF是垂体前叶促肾上腺皮质激素细胞的主要成分,并以激素样方式分泌到循环系统中。MIF也存在于单核细胞/巨噬细胞中,是宿主对内毒素休克反应的关键介质。为了进一步深入了解这种包含免疫和内分泌系统成分的蛋白质的生物学表达,我们克隆了小鼠MIF基因,并鉴定了5'-近端启动子区域内存在的潜在调控序列。小鼠MIF基因位于10号染色体上,跨度约1 kb,与其人类对应基因具有高度的结构同源性。值得注意的是,鉴定出的共有增强子/启动子基序包括炎症/生长因子相关元件以及与某些肽类激素基因相关的位点。我们还报告了两个MIF假基因的结构,这解释了早期的观察结果,即小鼠MIF由一个高度同源的多基因家族编码。