Diclofenac Inhibits IFN-γ Plus Lipopolysaccharide-Induced iNOS Gene Expression via Suppression of NF-κB Activation in RAW 264.7 Macrophages
Diclofenac Inhibits IFN-γ Plus Lipopolysaccharide-Induced iNOS Gene Expression via Suppression of NF-κB Activation in RAW 264.7 Macrophages
- So Hyun Bae Young Sue Ryu Jang Hee Hong Jin Chan Park Yong Man Kim Jeong Ho Seok Jae Heun Lee Gang M
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제5권 제6호
- 등재여부 : KCI등재
- 2001.01
- 521 - 527 (7 pages)
<P> 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.