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

Young J. Jeon, Seung H. Han, Yong W. Lee, Michael Lee, Kyu H. Yang, Hwan M. Kim

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)173-183
Number of pages11
JournalImmunopharmacology
Volume48
Issue number2
DOIs
StatePublished - Jul 20 2000

Keywords

  • AP-1
  • Dexamethasone
  • Glucocorticoid receptor
  • IL-1β
  • NF-κB/Rel

Fingerprint

Dive into the research topics of 'Dexamethasone inhibits IL-1β gene expression in LPS-stimulated RAW 264.7 cells by blocking NF-κB/Rel and AP-1 activation'. Together they form a unique fingerprint.

Cite this