Dependence and reversal of nitric oxide production on NF-kappa B in silica and lipopolysaccharide-induced macrophages

Biochem Biophys Res Commun. 1995 Sep 25;214(3):839-46. doi: 10.1006/bbrc.1995.2363.


In this report the differential regulation of NF-kappa B and nitric oxide (NO) was investigated in the mouse macrophage cell line RAW 264.7 following exposure to a mineral dust (silica) and/or an endotoxin (Lipopolysaccharide, LPS). The results indicated that silica and LPS can significantly induce the activation of NF-kappa B as well as elicit enhanced production of NO in RAW 264.7 cells as part of an early inflammatory response mechanism. A 24-hour time-course study showed that NO release from these cells continued to increase following the initial stimulus by LPS or silica. In contrast, activation of NF-kappa B was maximal at 6 hours and then showed a steady decline to 24 hours. The production of NO was suppressed by protease inhibitor and antioxidant, both of which block the activation of NF-kappa B. Surprisingly, the use of an NO synthase inhibitor resulted in an enhancement of NF-kappa B activation. These findings suggest that NO produced in macrophage cells in response to an inflammatory stimulus like silica or LPS my be linked to a negative feedback role on the activation of NF-kappa B.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcysteine / pharmacology
  • Alkaloids / pharmacology
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Base Sequence
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Enzyme Inhibitors / pharmacology
  • Indomethacin / pharmacology
  • Lipopolysaccharides / pharmacology*
  • Macrophage Activation*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Oligonucleotide Probes
  • Protein Kinase C / antagonists & inhibitors
  • Silicon Dioxide / pharmacology*
  • Staurosporine
  • Tosylphenylalanyl Chloromethyl Ketone / pharmacology
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology
  • omega-N-Methylarginine


  • Alkaloids
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • NF-kappa B
  • Oligonucleotide Probes
  • omega-N-Methylarginine
  • Nitric Oxide
  • benzoyltyrosine ethyl ester
  • Tosylphenylalanyl Chloromethyl Ketone
  • Tyrosine
  • Silicon Dioxide
  • Arginine
  • Nitric Oxide Synthase
  • Protein Kinase C
  • Staurosporine
  • Acetylcysteine
  • Indomethacin