TY - JOUR
T1 - Inhibition of NF-κB/Rel nuclear translocation by dexamethasone
T2 - Mechanism for the inhibition of iNOS gene expression
AU - Jeon, Young Jin
AU - Han, Seung Hyun
AU - Lee, Yong Woo
AU - Yea, Sung Su
AU - Yang, Kyu Hwan
PY - 1998/7
Y1 - 1998/7
N2 - The decrease in NO production was found to correlate well with a decrease in inducible nitric oxide synthase (iNOS) mRNA expression as demonstrated by Northern blot analysis and quantitative RT-PCR. Since the promoter in iNOS gene contains binding motifs for NF-κB/Rel, NF-IL6, and Oct which appear to be important for LPS-mediated iNOS induction, the effects of DEX on the activation of these transcription factors were examined. Treatment of DEX to RAW 264.7 cells induced a dose-related inhibition of NF-κB/Rel in chloramphenicol acetyltransferase activity, while NF-IL6 or Oct activation was not affected by DEX. Treatment of RAW 264.7 cells with DEX inhibited DNA binding of NF-κB/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, p65, and p50. These results suggest that DEX may inhibit iNOS gene expression by a mechanism involving the blockade of LPS-induced nuclear translocation of NF-κB/Rel.
AB - The decrease in NO production was found to correlate well with a decrease in inducible nitric oxide synthase (iNOS) mRNA expression as demonstrated by Northern blot analysis and quantitative RT-PCR. Since the promoter in iNOS gene contains binding motifs for NF-κB/Rel, NF-IL6, and Oct which appear to be important for LPS-mediated iNOS induction, the effects of DEX on the activation of these transcription factors were examined. Treatment of DEX to RAW 264.7 cells induced a dose-related inhibition of NF-κB/Rel in chloramphenicol acetyltransferase activity, while NF-IL6 or Oct activation was not affected by DEX. Treatment of RAW 264.7 cells with DEX inhibited DNA binding of NF-κB/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, p65, and p50. These results suggest that DEX may inhibit iNOS gene expression by a mechanism involving the blockade of LPS-induced nuclear translocation of NF-κB/Rel.
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U2 - 10.1080/15216549800202822
DO - 10.1080/15216549800202822
M3 - Article
C2 - 9679644
AN - SCOPUS:0031854198
SN - 1039-9712
VL - 45
SP - 435
EP - 441
JO - Biochemistry and Molecular Biology International
JF - Biochemistry and Molecular Biology International
IS - 3
ER -