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

Fingerprint

trichostatin A
Cyclooxygenase 2
Lipopolysaccharides
Assays
Phosphorylation
Histone Deacetylase Inhibitors
Chromatin
Chemical activation
Binding Sites
Cells

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Inhibition of LPS-induced C/EBPδ by trichostatin A has a positive effect on LPS-induced cyclooxygenase 2 expression in RAW264.7 cells. / Liu, Yi Wen; Wang, Shao An; Hsu, Tsung Yi; Chen, Tsu An; Chang, Wen Chang; Hung, Jan Jong.

In: Journal of Cellular Biochemistry, Vol. 110, No. 6, 15.08.2010, p. 1430-1438.

Research output: Contribution to journalArticle

@article{ac6104b169f3489cb62cb10311b82bdf,
title = "Inhibition of LPS-induced C/EBPδ by trichostatin A has a positive effect on LPS-induced cyclooxygenase 2 expression in RAW264.7 cells",
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.",
keywords = "C/EBPΔ, C/EBPα, C/EBPβ, Cyclooxygenase 2, Trichostatin A",
author = "Liu, {Yi Wen} and Wang, {Shao An} and Hsu, {Tsung Yi} and Chen, {Tsu An} and Chang, {Wen Chang} and Hung, {Jan Jong}",
year = "2010",
month = "8",
day = "15",
doi = "10.1002/jcb.22682",
language = "English",
volume = "110",
pages = "1430--1438",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Inhibition of LPS-induced C/EBPδ by trichostatin A has a positive effect on LPS-induced cyclooxygenase 2 expression in RAW264.7 cells

AU - Liu, Yi Wen

AU - Wang, Shao An

AU - Hsu, Tsung Yi

AU - Chen, Tsu An

AU - Chang, Wen Chang

AU - Hung, Jan Jong

PY - 2010/8/15

Y1 - 2010/8/15

N2 - 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.

AB - 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.

KW - C/EBPΔ

KW - C/EBPα

KW - C/EBPβ

KW - Cyclooxygenase 2

KW - Trichostatin A

UR - http://www.scopus.com/inward/record.url?scp=77955477207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955477207&partnerID=8YFLogxK

U2 - 10.1002/jcb.22682

DO - 10.1002/jcb.22682

M3 - Article

C2 - 20506344

AN - SCOPUS:77955477207

VL - 110

SP - 1430

EP - 1438

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 6

ER -