Diclofenac inhibits IFN-gamma plus lipopolysaccharide-induced iNOS gene expression via suppression of NF-kappaB activation in RAW 264.7 macrophages
The Korean Journal of Physiology and Pharmacology
; : 521-527, 2001.
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.
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