Korean J Physiol Pharmacol.  2001 Dec;5(6):521-527.

Diclofenac inhibits IFN-gamma plus lipopolysaccharide-induced iNOS gene expression via suppression of NF-kappaB activation in RAW 264.7 macrophages

• Bae SH
• Ryu YS
• Hong JH
• Park JC
• Kim YM
• Seok JH
• Lee JH
• Hur GM

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.

MeSH Terms

Animals
Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Cats
Diclofenac*
Gene Expression*
Genes, Reporter
Indomethacin
Inflammation
Interferon-gamma
Macrophages*
NF-kappa B*
Nitric Oxide
Nitric Oxide Synthase Type II
RNA, Messenger
Transfection
Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Diclofenac
Indomethacin
Interferon-gamma
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II
RNA, Messenger