Effect of quercetin on the production of nitric oxide in murine macrophages stimulated with lipopolysaccharide from Prevotella intermedia.
10.5051/jpis.2013.43.4.191
- Author:
Yun Jung CHO
1
;
Sung Jo KIM
Author Information
1. Department of Periodontology, Institute of Translational Dental Sciences, Pusan National University School of Dentistry, Yangsan, Korea. sungjokim@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
Lipopolysaccharides;
Nitric oxide;
Periodontal diseases;
Prevotella intermedia;
Quercetin
- MeSH:
Cell Culture Techniques;
Heme Oxygenase-1;
I-kappa B Proteins;
JNK Mitogen-Activated Protein Kinases;
Lipopolysaccharides;
Macrophages;
Metalloporphyrins;
Nitric Oxide;
Nitric Oxide Synthase;
Periodontal Diseases;
Phosphorylation;
Prevotella;
Prevotella intermedia;
Protoporphyrins;
Quercetin;
STAT1 Transcription Factor;
Tin
- From:Journal of Periodontal & Implant Science
2013;43(4):191-197
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Nitric oxide (NO) is a short-lived bioactive molecule that is known to play an important role in the pathogenesis of periodontal disease. In the current study, we investigated the effect of the flavonoid quercetin on the production of NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen related to inflammatory periodontal disease, and tried to elucidate the underlying mechanisms of action. METHODS: LPS was isolated from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The concentration of NO in cell culture supernatants was determined by measuring the accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38, inhibitory kappaB (IkappaB)-alpha degradation, and signal transducer and activator of transcription 1 (STAT1) phosphorylation were analyzed via immunoblotting. RESULTS: Quercetin significantly attenuated iNOS-derived NO production in RAW246.7 cells activated by P. intermedia LPS. In addition, quercetin induced HO-1 protein expression in cells activated with P. intermedia LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The degradation of IkappaB-alpha induced by P. intermedia LPS was inhibited when the cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1 signaling. CONCLUSIONS: Quercetin significantly inhibits iNOS-derived NO production in murine macrophages activated by P. intermedia LPS via anti-inflammatory HO-1 induction and inhibition of the nuclear factor-kappaB and STAT1 signaling pathways. Our study suggests that quercetin may contribute to the modulation of host-destructive responses mediated by NO and appears to have potential as a novel therapeutic agent for treating inflammatory periodontal disease.
