Induction of nitric oxide and nitric oxide synthase mRNA by silica and lipopolysaccharide in PMA-primed THP-1 cells.
Nitric oxide (NO), a nitrogen-free radical, plays an important role in mediating inflammatory reaction and cytotoxicity of tissue. To determine whether NO was involved in silica-induced pulmonary tissue damage, we studied the effects of silica on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression by THP-1 cells, a monocyte-like cell line with properties of the pulmonary alveolar macrophage. Experimental results showed that silica elicited a marked stimulation of nitric oxide production in a time-dependent manner by THP-1 cells in vitro following the priming of these cells with the phorbol ester PMA. Both nitric oxide synthase inhibitor N-monomethyl-L-arginine (NMMA) and xanthine oxidase inhibitor allopurinol can partially suppress silica-induced NO production in PMA-primed THP-1 cells. Northern blot analysis indicated that, after 2 h of silica exposure, PMA-primed THP-1 cells began to express iNOS mRNA, which reached peak expression at 8 h. Endotoxin treatment of these cells produced a similar effect. These results indicated that silica is a potent inducer of NO production in macrophages and its ability to induce tissue damage may partially be attributed to its ability to initiate excessive production of nitric oxide from macrophages.
Chen
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F
Department of Pathology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, USA.
Kuhn
D C
DC
Gaydos
L J
LJ
Demers
L M
LM
D000493:Allopurinol / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012822:Silicon Dioxide / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000502:physiology; D019323:omega-N-Methylarginine
D000963:Antimetabolites; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000493:Allopurinol; D012822:Silicon Dioxide; D001120:Arginine; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate