Inhibition of LPS-induced C/EBPδ by trichostatin A has a positive effect on LPS-induced cyclooxygenase 2 expression in RAW264.7 cells

Yi Wen Liu, Shao An Wang, Tsung Yi Hsu, Tsu An Chen, Wen Chang Chang, Jan Jong Hung

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cyclooxygenase 2 (COX-2) is an important inflammatory factor. Previous studies have indicated that COX-2 is induced with lipopolysaccharide (LPS) treatment. Here, we found that an inhibitor of histone deacetylase (HDAC), trichostatin A (TSA), cannot repress LPS-induced COX-2 but it increased the COX-2 level in RAW264.7 cells. We found no significant difference in NF-κB activation and ERK1/2 phosphorylation, but LPS-induced C/EBPδ expression was completely abolished after TSA treatment of LPS-treated cells. Interesting, reporter assay of C/EBPδ promoter revealed that Sp1-binding site is important. Although there was no alteration in c-Jun levels, but the phosphorylation of c-Jun at its C-terminus was increased dramatically. A DNA-associated protein assay (DAPA) and chromatin immuno-precipitation assay (ChIP) indicated that c-Jun was recruited via Sp1 to the promoter of C/EBPδ after LPS treatment; this recruitment of c-Jun was repressed by TSA. C/EBPδ inhibition by TSA resulted in increased binding of C/EBPα and C/EBPβ to the COX-2 promoter. Therefore, TSA has a positive effect on LPS-induced COX-2 since it decreases the C/EBPδ level by reducing c-Jun recruitment by Sp1 to the C/EBPδ promoter, resultinginincreased the recruitment of C/EBPα and C/EBPβ to the COX-2 promoter.

Original languageEnglish
Pages (from-to)1430-1438
Number of pages9
JournalJournal of Cellular Biochemistry
Volume110
Issue number6
DOIs
Publication statusPublished - Aug 15 2010

Keywords

  • C/EBPΔ
  • C/EBPα
  • C/EBPβ
  • Cyclooxygenase 2
  • Trichostatin A

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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