INHIBITION OF NF-KAPPA-B REL NUCLEAR TRANSLOCATION BY DEXAMETHASONE -MECHANISM FOR THE INHIBITION OF INOS GENE-EXPRESSION/

Citation
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
Citations number
13
Categorie Soggetti
Biology
ISSN journal
10399712
Volume
45
Issue
3
Year of publication
1998
Pages
435 - 441
Database
ISI
SICI code
1039-9712(1998)45:3<435:IONRNT>2.0.ZU;2-#
Abstract
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.