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Biochem Pharmacol ; 72(8): 1001-9, 2006 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-16930561

RESUMEN

Pectin is composed of complex polysaccharides rich in galactoside residues, and it is most abundant in citrus fruits. Pectin and modified pectin have been found to exhibit anti-mutagenic activity and inhibit cancer metastasis and proliferation, with no evidence of toxicity or other serious side effects. In this study, we investigated the inhibitory effect of pectin at different degrees of esterification (DEs) on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-activated macrophages. Western blot and RT-PCR analyses demonstrated that 30% esterified pectin (DE30), DE60 pectin, and DE90 pectin significantly inhibited the protein and mRNA expressions of iNOS and COX-2 in LPS-activated macrophages, and DE90 pectin was the most-potent inhibitor. To clarify the mechanisms involved, DE90 pectin was found to inhibit the phosphorylation of MAPKs and IKK kinase activity. In addition, DE90 pectin inhibited the activation of NF-kappaB and AP-1 by electrophoretic mobility shift assay and transient transfection experiments. Finally, we found that DE90 pectin could bind with LPS, and might result in decreased binding of LPS to its receptor. These results suggest that modulation of iNOS and COX-2 expressions by dietary pectin may be important in cancer chemoprevention and anti-inflammation.


Asunto(s)
Inhibidores de la Ciclooxigenasa 2/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Pectinas/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citrus , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Proteínas I-kappa B/metabolismo , Inflamación/inducido químicamente , Inflamación/prevención & control , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Inhibidor NF-kappaB alfa , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo
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