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

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-kappaB (NF-kappaB) and CCAAT/enhancer-binding protein beta (C/EBPbeta), 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/EBPbeta DNA-binding activity and NF-kappaB activation.

• Authors: Young-Ho Kim, Kyung Jin Woo, Jun Hee Lim, Shin Kim, Tae Jin Lee, Eun Mi Jung, Jin-Man Lee, Jong-Wook Park, Taeg Kyu Kwon
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 329 Issue 2 Pg. 591-7 (Apr 08 2005) ISSN: 0006-291X [Print] United States
• PMID: 15737626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCAAT-Enhancer-Binding Proteins
• Ddit3 protein, mouse
• Enzyme Inhibitors
• Lipopolysaccharides
• NF-kappa B
• Transcription Factors
• Transcription Factor CHOP
• Nitric Oxide
• Oxyquinoline
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Animals
• CCAAT-Enhancer-Binding Proteins (metabolism)
• Cell Line
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects, physiology)
• Drug Interactions
• Enzyme Activation (drug effects)
• Enzyme Inhibitors
• Gene Expression Regulation, Enzymologic (drug effects, physiology)
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects, metabolism)
• Mice
• NF-kappa B (metabolism)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type II
• Oxyquinoline (pharmacology)
• Transcription Factor CHOP
• Transcription Factors (metabolism)