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

Int Immunol. 1998 Dec;10(12):1825-35. doi: 10.1093/intimm/10.12.1825.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Binding Sites / immunology
  • CCAAT-Enhancer-Binding Proteins
  • Chemokine CCL4
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Leukemic / immunology*
  • Humans
  • Leukemia, Monocytic, Acute / genetics*
  • Leukemia, Monocytic, Acute / immunology
  • Leukemia, Monocytic, Acute / metabolism*
  • Lipopolysaccharide Receptors / biosynthesis*
  • Lipopolysaccharide Receptors / genetics
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophage Inflammatory Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Muramidase / biosynthesis
  • Muramidase / genetics
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Osteopontin
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Sialoglycoproteins / biosynthesis*
  • Sialoglycoproteins / genetics
  • Transcriptional Activation / immunology
  • Tumor Cells, Cultured

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Chemokine CCL4
  • DNA-Binding Proteins
  • Lipopolysaccharide Receptors
  • Macrophage Inflammatory Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • SPP1 protein, human
  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Osteopontin
  • Muramidase