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Int. Immunol. Dec (1998); 10(12):1825-35
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.
Matsumoto M, Sakao Y, Akira S
Department of Biochemistry, Hyogo College of Medicine, Japan.
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.
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.