Essential Role of NF-κB Activation in Silica-Induced Inflammatory Mediator Production in Macrophages

In this report, we demonstrate that NF-κB, a ubiquitous transcription factor, plays an essential role in silica-induced inflammatory mediator production in the mouse macrophage cell line RAW 264.7. Compared to the effect of lipopolysaccharide (LPS), silica mediated a stronger activation of NF-κB p50...

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Published in:	Biochemical and biophysical research communications Vol. 214; no. 3; pp. 985 - 992
Main Authors:	Chen, F., Sun, S.C., Kuh, D.C., Gaydos, L.J., Demers, L.M.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 25-09-1995
Subjects:	Animals Arginine - analogs & derivatives Arginine - pharmacology Base Sequence Cell Line Consensus Sequence DNA - biosynthesis Enzyme Induction - drug effects Gene Expression - drug effects Inflammation Interleukin-1 - biosynthesis Isoenzymes - biosynthesis Lipopolysaccharides - pharmacology Macrophages, Alveolar - drug effects Macrophages, Alveolar - metabolism Mice Molecular Sequence Data NF-kappa B - metabolism Nitric Oxide Synthase - biosynthesis Oligodeoxyribonucleotides omega-N-Methylarginine Prostaglandin-Endoperoxide Synthases - biosynthesis Protease Inhibitors - pharmacology RNA, Messenger - biosynthesis Silicon Dioxide - pharmacology Tosylphenylalanyl Chloromethyl Ketone - pharmacology Transcription, Genetic Tumor Necrosis Factor-alpha - biosynthesis Tyrosine - analogs & derivatives Tyrosine - pharmacology
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Summary:	In this report, we demonstrate that NF-κB, a ubiquitous transcription factor, plays an essential role in silica-induced inflammatory mediator production in the mouse macrophage cell line RAW 264.7. Compared to the effect of lipopolysaccharide (LPS), silica mediated a stronger activation of NF-κB p50/p50 homodimer at early phase of poststimulation. Furthermore, activation of NF-κB by silica and LPS appears to be mediated by different signal transduction pathways. Both silica and LPS increased mRNA expression in these cells for cyclooxygenase II, inducible nitric oxide synthase, tumor necrosis factor-α and interleukin-1α. This expression was attenuated along with the inhibition of NF-κB activation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-291X 1090-2104
DOI:	10.1006/bbrc.1995.2383