Yj. Jeon et al., INHIBITION OF NF-KAPPA-B REL NUCLEAR TRANSLOCATION BY DEXAMETHASONE -MECHANISM FOR THE INHIBITION OF INOS GENE-EXPRESSION/, Biochemistry and molecular biology international, 45(3), 1998, pp. 435-441
The decrease in NO production was found to correlate well with a decre
ase in inducible nitric oxide synthase (iNOS) mRNA expression as demon
strated by Northern blot analysis and quantitative RT-PCR. Since the p
romoter in iNOS gene contains binding motifs for NF-kappa B/Rel, NF-IL
6, and Oct which appear to be important for LFS-mediated iNOS inductio
n, the effects of DEX on the activation of these transcription factors
were examined. Treatment of DEX to RAW 264.7 cells induced a dose-rel
ated inhibition of NF-kappa B/Rel in chloramphenicol acetyltransferase
activity, while NF-IL6 or Oct activation was not affected by DEX. Tre
atment of RAW 264.7 cells with DEX inhibited DNA binding of NF-kappa B
/Rel proteins to their cognate DNA site as measured by electrophoretic
mobility shift assay. In addition, DEX treatment caused a significant
reduction in nuclear c-rel, p65, and p50 protein contents, and these
decreases were paralleled by the accumulation of cytoplasmic c rel, p6
5, and p50. These results suggest that DEX may inhibit iNOS gene expre
ssion by a mechanism involving the blockade of LPS-induced nuclear tra
nslocation of NF-kappa B/Rel.