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8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down-regulating LPS-induced activity of NF-κB and C/EBPβ in Raw 264.7 cells

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Author(s)
Young-Ho KimKyung Jin WooJun Hee LimShin KimTae Jin LeeEun Mi JungJin-Man LeeJong-Wook ParkTaeg Kyu Kwon
Publication Year
2005
Abstract
In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, 8-hydroxyquinoline (8HQ) inhibited the LPS-induced expression of both iNOS protein and mRNA in a parallel dose-dependent manner. 8HQ did not enhance the degradation of iNOS mRNA. To investigate the mechanism by which 8HQ inhibits iNOS gene expression, we examined the activation of MAP kinases in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between LPS alone and LPS plus 8HQ-treated cells. Moreover, 8HQ significantly inhibited the DNA-binding activity of nuclear factor-κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), but not activator protein-1 and cAMP response element-binding protein. Taken together, these results suggest that 8HQ acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of C/EBPβ DNA-binding activity and NF-κB activation.

Keywords
8HQ;
Nitric oxide;
iNOS;
NF-κB;
C/EBPβ
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.329(2) : 591-597, 2005
Type
Article
ISSN
0006-291X
DOI
10.1016/j.bbrc.2005.01.159
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35153
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