Liu Hongtao, Shi Bo, Huang Chiang-Ching, Eksarko Polikseni, Pope Richard M
Northwestern University Feinberg School of Medicine, Division of Rheumatology, Chicago, IL 60611, United States.
Immunol Lett. 2008 Apr 15;117(1):70-80. doi: 10.1016/j.imlet.2007.12.012. Epub 2008 Jan 22.
Monocytes recruited into tissues from peripheral blood differentiate into macrophages, which are critical in the pathogenesis of many diseases. There is limited data concerning the global changes in the expression of genes during monocyte to macrophage differentiation, and how the patterns of change identify the mechanism contributing to macrophage differentiation or function. Employing microarray technology, we examined the transcriptional profile of in vitro adherence-induced differentiation of primary human monocytes into macrophages. We found the significant up regulation of genes contributing to the functions of macrophages, including those regulating to immunity and defense; lipid, fatty acid and steroid metabolism; cell adhesion, carbohydrate metabolism; amino acid metabolism and endocytosis. In contrast, the vast majority of transcription factors affected were down regulated during monocyte to macrophage differentiation, suggesting that transcriptional repression may be important for the transition from monocytes to macrophages. However, a limited number of transcription factors were up regulated, among these was C/EBPalpha, which may contribute to differentiation by regulating down stream genes, which are a characteristic of differentiated macrophages. These observations suggest that examination of the transcriptional profile in monocytes and macrophages in patients may identify relevant therapeutic targets in diseases mediated by macrophages.
从外周血募集到组织中的单核细胞分化为巨噬细胞，巨噬细胞在许多疾病的发病机制中起关键作用。关于单核细胞向巨噬细胞分化过程中基因表达的整体变化，以及这些变化模式如何确定促成巨噬细胞分化或功能的机制，相关数据有限。利用微阵列技术，我们检测了原代人单核细胞体外黏附诱导分化为巨噬细胞的转录谱。我们发现，对巨噬细胞功能有贡献的基因显著上调，包括那些调节免疫与防御、脂质、脂肪酸和类固醇代谢、细胞黏附、碳水化合物代谢、氨基酸代谢以及内吞作用的基因。相比之下，在单核细胞向巨噬细胞分化过程中，绝大多数受影响的转录因子下调，这表明转录抑制可能对单核细胞向巨噬细胞的转变很重要。然而，有少数转录因子上调，其中包括C/EBPα，它可能通过调节下游基因来促进分化，而这些下游基因是分化巨噬细胞的特征。这些观察结果表明，检测患者单核细胞和巨噬细胞中的转录谱可能会确定由巨噬细胞介导的疾病中的相关治疗靶点。
