Diclofenac Inhibits $IFN-{\gamma}$ Plus Lipopolysaccharide-Induced iNOS Gene Expression via Suppression of $NF-{\kappa}B$ Activation in RAW 264.7 Macrophages

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 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 Also, diclofenac but not aspirin and indomethacin, inhibited iNOS mRNA expression and nuclear factor-kappa B 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 through the 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 activation.