Inducible expression of nuclear factor IL-6 increases endogenous gene expression of macrophage inflammatory protein-1 alpha, osteopontin and CD14 in a monocytic leukemia cell line.
Nuclear factor-IL-6 (NF-IL6) belongs to the CCAAT/enhancer binding protein family of transcription factors. NF-IL6 binds to the regulatory regions of many genes induced in activated macrophages in vitro. However, which particular genes are regulated by NF-IL6 in vivo is poorly defined. In order to identify the downstream genes of NF-IL6 in a monocytic lineage, we combined an inducible expression system with subtraction cloning in a study of murine M1 monocytic leukemia cells. We demonstrated that inducible expression of NF-IL6 is able to increase endogenous gene expression of macrophage inflammatory protein (MIP)-1 alpha, osteopontin and CD14 in M1 cells. We also showed that NF-IL6 activated murine MIP-1 alpha proximal promoter luciferase construct which contains two NF-IL6 binding sites and a point mutation of either site markedly reduces the luciferase activity. These findings indicate that MIP-1 alpha is a direct target of NF-IL6.
Matsumoto
M
M
Department of Biochemistry, Hyogo College of Medicine, Japan.
Sakao
Y
Y
Akira
S
S
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D022762:CCAAT-Enhancer-Binding Proteins; D054407:Chemokine CCL4; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology*; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D053495:Osteopontin; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation / Q000276:immunology; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D054407:Chemokine CCL4; D004268:DNA-Binding Proteins; D018950:Lipopolysaccharide Receptors; D019402:Macrophage Inflammatory Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D009113:Muramidase