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KMID : 0811720010050060521
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Korean Journal of Physiology & Pharmacology
2001 Volume.5 No. 6 p.521 ~ p.527
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Diclofenac Inhibits IFN-γ Plus Lipopolysaccharide-Induced iNOS Gene Expression via Suppression of NF-κB Activation in RAW 264.7 Macrophages
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So Hyun Bae
Young Sue Ryu/Jang Hee Hong/Jin Chan Park/Yong Man Kim*/Jeong Ho Seok/Jae Heun Lee/Gang Min Hur
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Abstract
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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?γ). 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?γ. Also, diclofenac but not aspirin and indomethacin, inhibited iNOS mRNA expression and nuclear factor-kappa B (NF?κB) 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?γ through the NF?κB 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?κB activation.
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KEYWORD
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Diclofenac, NSAIDs, iNOS, NF-κB binding site, Macrophages,
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