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.
Artigo
em Inglês
| WPRIM
| ID: wpr-728778
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:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
RNA Mensageiro
/
Transfecção
/
Expressão Gênica
/
Anti-Inflamatórios não Esteroides
/
Aspirina
/
Diclofenaco
/
Indometacina
/
NF-kappa B
/
Interferon gama
/
Genes Reporter
Limite:
Animais
Idioma:
Inglês
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2001
Tipo de documento:
Artigo
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