Quinazoline derivatives suppress nitric oxide production by macrophages through inhibition of NOS II gene expression.
We have found three novel quinazolidine derivatives which inhibit the formation of nitrite dose-dependently in a murine macrophage cell line, RAW264.7. The decreased nitrite formation was due not to the inhibition of nitric oxide synthase activity but to suppression of NOS II mRNA and protein expression. In rat vascular smooth muscle cells (VSMC), however, these compounds rather enhanced NOS II mRNA. These compounds also prevented LPS-stimulated heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) gene expression in RAW264.7 cells, but again not in VSMC. The three quinazolidine derivatives specifically inhibit gene expression of NOS II, HO-1 and COX-2 only in macrophage cells, indicating that they are selective inhibitors of inducible gene expression in macrophages.
Department of Biochemistry, Osaka University Medical School, Japan.
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N
Fujiwara
A
A
Okado
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HG
Seo
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J
Fujii
K
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Kondo
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Taniguchi
D000818:Animals; D001011:Aorta; D002460:Cell Line; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*
D007527:Isoenzymes; D008070:Lipopolysaccharides; D011799:Quinazolines; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases