2-Amino-3-methylimidazo[4,5-f]quinoline inhibits nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells by blocking p38 kinase activation

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Title
2-Amino-3-methylimidazo[4,5-f]quinoline inhibits nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells by blocking p38 kinase activation
Author(s)
Yong W Lee; Seung H Han; Michael Lee; Kyu H Yang; Hwan Mook Kim; Yong Jin Jeon
Bibliographic Citation
Cancer Letters, vol. 156, no. 2, pp. 133-139
Publication Year
2000
Abstract
We show that 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic amine, significantly inhibits nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages. The decrease in NO production was found to correlate well with a decrease in inducible NO synthase (iNOS) mRNA expression as demonstrated by Northern blot analysis. Treatment of RAW 264.7 cells with IQ selectively inhibited the activation of NF-κB/Rel, an important transcription factor of iNOS gene expression, while neither AP-1 nor Oct was affected by IQ. Since iNOS transcription has been shown recently to be under the control of the p38 kinase signaling cascade, we assessed the effect of IQ on p38 kinase activation. Treatment of RAW 264.7 with IQ inhibited LPS-stimulated p38 kinase phosphorylation in a dose-related manner. IQ also inhibited the p38 kinase activity. Collectively, this series of experiments indicates that IQ inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Based on our findings, the most likely mechanism that can account for this biological effect involves the negative regulation of NF-κB/Rel and p38 kinase pathway.
Keyword
2-Amino-3-methylimidazo[4,5-f]quinolineiNOSNF-κB/Relp38 MAPK
ISSN
0304-3835
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S0304-3835(00)00452-3
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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