Essential role of NF-kappa B activation in silica-induced inflammatory mediator production in macrophages.
In this report, we demonstrate that NF-kappa B, 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-kappa B p50/p50 homodimer at early phase of poststimulation. Furthermore, activation of NF-kappa B 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-alpha and interleukin-1 alpha. This expression was attenuated along with the inhibition of NF-kappa B activation.
Chen
F
F
Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Sun
S C
SC
Kuh
D C
DC
Gaydos
L J
LJ
Demers
L M
LM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D016384:Consensus Sequence; D004247:DNA / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D009838:Oligodeoxyribonucleotides; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012822:Silicon Dioxide / Q000494:pharmacology*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019323:omega-N-Methylarginine
D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; C006716:benzoyltyrosine ethyl ester; D014108:Tosylphenylalanyl Chloromethyl Ketone; D014443:Tyrosine; D012822:Silicon Dioxide; D004247:DNA; D001120:Arginine; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases