Abstract
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
Substances
-
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