Dependence and reversal of nitric oxide production on NF-kappa B in silica and lipopolysaccharide-induced macrophages.
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.
Chen
F
F
Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Kuhn
D C
DC
Sun
S C
SC
Gaydos
L J
LJ
Demers
L M
LM
D000111:Acetylcysteine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015345:Oligonucleotide Probes; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012822:Silicon Dioxide / Q000494:pharmacology*; D019311:Staurosporine; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019323:omega-N-Methylarginine
D000470:Alkaloids; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C006716:benzoyltyrosine ethyl ester; D014108:Tosylphenylalanyl Chloromethyl Ketone; D014443:Tyrosine; D012822:Silicon Dioxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D019311:Staurosporine; D000111:Acetylcysteine; D007213:Indomethacin