Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by tropolones.
We investigated the effect of 27 tropolones on nitric oxide (NO) production by mouse macrophage-like Raw 264.7 cells. All of these compounds failed to stimulate the Raw 264. 7 cells to produce detectable amounts of NO, but inhibited NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to various extents. Generally, the ability of tropolones to inhibit LPS-stimulated NO production was inversely related to their cytotoxic activity. Western blot and RT-PCR analyses demonstrated that the most active compound, 2,4-dibromo-7-methoxytropone [21], significantly reduced both the intracellular concentration of iNOS protein and the expression of iNOS mRNA. ESR spectroscopy showed that [21] did not produce radicals under alkaline condition, nor scavenged NO, produced by NOC-7. These data suggested that the inhibitory effect of [21] on NO production might be generated via the inhibition of iNOS expression, rather than a radical-mediated mechanism.
Yokoyama
Keiko
K
Faculty of Science, Josai University, Sakado, Saitama, Japan.
Hashiba
Kana
K
Wakabayashi
Hidetsugu
H
Hashimoto
Ken
K
Satoh
Kazue
K
Kurihara
Teruo
T
Motohashi
Noboru
N
Sakagami
Hiroshi
H
D000818:Animals; D001565:Benzoates / Q000737:chemistry; D015153:Blotting, Western; D004347:Drug Interactions; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019097:Spin Trapping; D013329:Structure-Activity Relationship; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology
D001565:Benzoates; D016166:Free Radical Scavengers; D007093:Imidazoles; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D014334:Tropolone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse