Diclofenac inhibits IFN-gamma plus lipopolysaccharide-induced iNOS gene expression via suppression of NF-kappaB activation in RAW 264.7 macrophages.
- Author:
So Hyun BAE
1
;
Young Sue RYU
;
Jang Hee HONG
;
Jin Chan PARK
;
Yong Man KIM
;
Jeong Ho SEOK
;
Jae Heun LEE
;
Gang Min HUR
Author Information
1. Department of Pharmacology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-131, Korea. gmhur@hanbat.chungnam.ac.kr
- Publication Type:Original Article
- MeSH:
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
- From:The Korean Journal of Physiology and Pharmacology
2001;5(6):521-527
- CountryRepublic of Korea
- Language:English
-
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.
