Dexamethasone inhibits IL-1β gene expression in LPS-stimulated RAW 264.7 cells by blocking NF-κB/Rel and AP-1 activation

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Title
Dexamethasone inhibits IL-1β gene expression in LPS-stimulated RAW 264.7 cells by blocking NF-κB/Rel and AP-1 activation
Author(s)
Young Jin Jeon; Seung H Han; Yong W Lee; Michael Lee; Kyu H Yang; Hwan Mook Kim
Bibliographic Citation
Immunopharmacology, vol. 48, no. 2, pp. 173-183
Publication Year
2000
Abstract
In the present study, the mechanism by which dexamethasone (DEX) inhibited IL-1β gene expression in bacterial lipopolysaccharide (LPS)-activated RAW 264.7 cells was investigated. The decrease in LPS-induced IL-1β mRNA expression was demonstrated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Since the promoter in IL-1β gene contains binding motifs for NF-κB/Rel, AP-1, NF-IL6, and CREB/ATF, which appear to be important in LPS-mediated IL-1β 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 and AP-1 in chloramphenicol acetyltransferase activity, while neither NF-IL6 nor CREB/ATF activation was affected by DEX. Treatment of RAW 264.7 cells with DEX inhibited DNA binding of NF-κB/Rel and AP-1 proteins to their cognate DNA sites as measured by electrophoretic mobility shift assay (EMSA). 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. DEX treatment of RAW 264.7 cells did not inhibit the nuclear translocation of c-jun and c-fos. We found that the inhibition of IL-1β production by DEX is not related to p38, which is important in the IL-1β induction. These results suggest that DEX may inhibit IL-1β gene expression by a mechanism involving the blocking of LPS-induced NF-κB/Rel and AP-1 activation.
Keyword
dexamethasoneIL-1βNF-κB/RelAP-1glucocorticoid receptor
ISSN
0162-3109
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S0162-3109(00)00199-5
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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