Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Binding Sites / genetics
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Binding Sites / immunology
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CCAAT-Enhancer-Binding Proteins
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Chemokine CCL4
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Gene Expression Regulation, Leukemic / immunology*
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Humans
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Leukemia, Monocytic, Acute / genetics*
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Leukemia, Monocytic, Acute / immunology
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Leukemia, Monocytic, Acute / metabolism*
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Lipopolysaccharide Receptors / biosynthesis*
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Lipopolysaccharide Receptors / genetics
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Macrophage Inflammatory Proteins / biosynthesis
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Macrophage Inflammatory Proteins / genetics*
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Mice
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Molecular Sequence Data
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Muramidase / biosynthesis
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Muramidase / genetics
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Nuclear Proteins / biosynthesis*
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Nuclear Proteins / genetics
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Osteopontin
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Promoter Regions, Genetic
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RNA, Messenger / metabolism
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Sialoglycoproteins / biosynthesis*
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Sialoglycoproteins / genetics
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Transcriptional Activation / immunology
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Tumor Cells, Cultured
Substances
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CCAAT-Enhancer-Binding Proteins
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Chemokine CCL4
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DNA-Binding Proteins
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Lipopolysaccharide Receptors
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Macrophage Inflammatory Proteins
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Nuclear Proteins
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RNA, Messenger
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SPP1 protein, human
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Sialoglycoproteins
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Spp1 protein, mouse
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Osteopontin
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Muramidase