Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor cytotoxicity by macrophages

Cell. 1995 Jan 27;80(2):353-61. doi: 10.1016/0092-8674(95)90418-2.

Abstract

To investigate the role of NF-IL6 in vivo, we have generated NF-IL6 (-/-) mice by gene targeting. NF-IL6 (-/-) mice were highly susceptible to infection by Listeria monocytogenes. Electron microscopic observation revealed the escape of a larger number of pathogens from the phagosome to the cytoplasm in activated macrophages from NF-IL6 (-/-) mice. Furthermore, the tumor cytotoxicity of macrophages from NF-IL6 (-/-) mice was severely impaired. However, cytokines involved in macrophage activation, such as TNF and IFN gamma, were induced normally in NF-IL6 (-/-) mice. Nitric oxide (NO) formation was induced to a similar extent in macrophages from both wild-type and NF-IL6 (-/-) mice. These results demonstrate the crucial role of NF-IL6 in macrophage bactericidal and tumoricidal activities as well as the existence of a NO-independent mechanism of these activities. We also demonstrate that NF-IL6 is essential for the induction of G-CSF in macrophages and fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Base Sequence
  • Biological Assay
  • CCAAT-Enhancer-Binding Proteins
  • Cytotoxicity, Immunologic*
  • DNA Primers
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Granulocyte Colony-Stimulating Factor / analysis
  • Granulocyte Colony-Stimulating Factor / biosynthesis
  • Hydrogen Peroxide / metabolism
  • Interferon-gamma / pharmacology
  • Interleukin-6 / physiology
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology*
  • Macrophage Activation
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / physiology*
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / physiology
  • Polymerase Chain Reaction
  • Stem Cells
  • Superoxides / metabolism
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology
  • omega-N-Methylarginine

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Interleukin-6
  • Nuclear Proteins
  • Tumor Necrosis Factor-alpha
  • Superoxides
  • Granulocyte Colony-Stimulating Factor
  • omega-N-Methylarginine
  • Nitric Oxide
  • Interferon-gamma
  • Arginine
  • Hydrogen Peroxide