International Immunology, Vol 10, 1825-1835, Copyright © 1998 by Oxford University Press
M Matsumoto, Y Sakao and S Akira
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)- 1alpha, osteopontin and CD14 in M1
cells. We also showed that NF-IL6 activated murine MIP-1alpha 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-1alpha is a direct target of NF-IL6.
ARTICLES
Inducible expression of nuclear factor IL-6 increases endogenous gene expression of macrophage inflammatory protein-1alpha, osteopontin and CD14 in a monocytic leukemia cell line
Department of Biochemistry, Hyogo College of Medicine, Japan.
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