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Diclofenac inhibits IFN-gamma plus lipopolysaccharide-induced iNOS gene expression via suppression of NF-kappaB activation in RAW 264.7 macrophages
Article en En | WPRIM | ID: wpr-728778
Biblioteca responsable: WPRO
ABSTRACT
Diclofenac, a phenylacetic acid derivative, is a widely used non-steroidal anti-inflammatory drug (NSAID) to provide effective relief of inflammation and pain. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. We examined the inhibitory effects of diclofenac on the induction of iNOS in RAW 264.7 macrophages which were activated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). Treatment of RAW 264.7 cells with diclofenac and other NSAIDs (aspirin and indomethacin) significantly inhibited NO production and iNOS protein expression induced by LPS plus IFN-gamma. Also, diclofenac but not aspirin and indomethacin, inhibited iNOS mRNA expression and nuclear factor-kappa B (NF-kappaB) binding activity concentration-dependently. Furthermore, transfection of RAW 264.7 cells with iNOS promoter linked to a CAT reporter gene revealed that only diclofenac inhibited the iNOS promoter activity induced by LPS plus IFN-gamma through the NF-kappaB sites of iNOS promoter. Taken together, these suggest that diclofenac may exert its anti-inflammatory effect by inhibiting iNOS gene expression at the transcriptional level through suppression of NF-kappaB activation.
Asunto(s)
Texto completo: 1 Índice: WPRIM Asunto principal: ARN Mensajero / Transfección / Expresión Génica / Antiinflamatorios no Esteroideos / Aspirina / Diclofenaco / Indometacina / FN-kappa B / Interferón gamma / Genes Reporteros Límite: Animals Idioma: En Revista: The Korean Journal of Physiology and Pharmacology Año: 2001 Tipo del documento: Article
Texto completo: 1 Índice: WPRIM Asunto principal: ARN Mensajero / Transfección / Expresión Génica / Antiinflamatorios no Esteroideos / Aspirina / Diclofenaco / Indometacina / FN-kappa B / Interferón gamma / Genes Reporteros Límite: Animals Idioma: En Revista: The Korean Journal of Physiology and Pharmacology Año: 2001 Tipo del documento: Article