Monocyte differentiation to macrophage requires interferon regulatory factor 7.
Interferon regulatory factors are a growing family of transcription factor that have been implicated in cellular events such as cell-growth regulation, antiviral defense, and development of the immune system. Interferon regulatory factor 7 (IRF-7) is expressed predominantly in lymphoid tissues and has been studied extensively in the context of viral infection and the induction of interferon and cytokine gene expression. In this paper, the involvement of IRF-7 in monocyte differentiation was examined in U937, HL60, and human primary macrophages. We report the induction of IRF-7 expression by 12-O-tetradecanoylphorbol-13-acetate in U937 and HL60 cells and demonstrate that this induction is essential for the monocyte differentiation to macrophages. We show that the monocyte differentiation is inhibited in cells expressing a dominant negative IRF-7 mutant, as evidenced by decreased expression of two macrophage-differentiation markers, CD11b and CD11c, and impaired phagocytic activity. In addition, we demonstrate that overexpression of IRF-7 is sufficient to trigger monocyte differentiation and to induce cell cycle arrest. The identification of IRF-7 as a key regulator in monocyte differentiation suggests a novel function of IRF-7 in innate immunity.
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Oncology Center and the Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
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D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D050839:Interferon Regulatory Factor-7; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D010587:Phagocytosis; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D020298:U937 Cells
D004268:DNA-Binding Proteins; C494234:IRF7 protein, human; D016167:Integrin alphaXbeta2; D050839:Interferon Regulatory Factor-7; D016177:Macrophage-1 Antigen