Kota Rama S, Rutledge John C, Gohil Kishorchandra, Kumar Aseem, Enelow Richard I, Ramana Chilakamarti V
Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, University of California at Davis, Davis, CA 95616, USA.
Biochem Biophys Res Commun. 2006 Apr 21;342(4):1137-46. doi: 10.1016/j.bbrc.2006.02.087. Epub 2006 Feb 24.
Macrophages play an important role in immune responses and in inflammatory disease states such as atherosclerosis. Interferon-gamma (IFN-gamma) is a major cytokine involved in the activation of macrophages. To elucidate the primary response of various genes and biological pathways regulated by IFN-gamma in macrophage, we analyzed the gene expression profile in RAW 264.7 macrophage cells treated with IFN-gamma for 4h. Microarray analysis revealed that about 400 genes were differentially expressed, of which about 250 genes were up-regulated and 150 were down-regulated. Functional organization of the transcriptome revealed that induced genes are involved in antimicrobial and antiviral responses, antigen presentation, chemokine and cytokine signaling, and inhibition of cell growth. We also found that expression of genes involved in cell-cycle control, DNA repair, and lipid metabolism was suppressed by IFN-gamma. We also identified induction of multiple transcription factors by IFN-gamma in RAW 264.7 cells. Functional annotation of genes regulated by IFN-gamma in RAW 264.7 cells may provide novel insights into the role of macrophages in immunity and in inflammatory disease.
巨噬细胞在免疫反应以及动脉粥样硬化等炎症性疾病状态中发挥着重要作用。γ干扰素(IFN-γ)是参与巨噬细胞激活的主要细胞因子。为了阐明IFN-γ在巨噬细胞中调控的各种基因和生物学途径的初始反应,我们分析了用IFN-γ处理4小时的RAW 264.7巨噬细胞中的基因表达谱。微阵列分析显示约400个基因存在差异表达,其中约250个基因上调,150个基因下调。转录组的功能组织显示,诱导基因参与抗菌和抗病毒反应、抗原呈递、趋化因子和细胞因子信号传导以及细胞生长抑制。我们还发现,IFN-γ抑制了参与细胞周期控制、DNA修复和脂质代谢的基因的表达。我们还在RAW 264.7细胞中鉴定出IFN-γ诱导的多种转录因子。RAW 264.7细胞中受IFN-γ调控的基因的功能注释可能为巨噬细胞在免疫和炎症性疾病中的作用提供新的见解。