LPS-induced G-CSF expression in macrophages is mediated by ERK2, but not ERK1

Shwu Fen Chang, Shih Shan Lin, Hui Ching Yang, Yuan Yi Chou, Jhen I. Gao, Shao Chun Lu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Granulocyte colony-stimulating factor (G-CSF) selectively stimulates proliferation and differentiation of neutrophil progenitors which play important roles in host defense against infectious agents. However, persistent G-CSF production often leads to neutrophilia and excessive inflammatory reactions. There is therefore a need to understand the mechanism regulating G-CSF expression. In this study, we showed that U0126, a MEK1/2 inhibitor, decreases lipopolysaccharide (LPS)-stimulated G-CSF promoter activity, mRNA expression and protein secretion. Using short hairpin RNA knockdown, we demonstrated that ERK2, and not ERK1, involves in LPS-induced G-CSF expression, but not LPS-regulated expression of TNF-α. Reporter assays showed that ERK2 and C/EBPβ synergistically activate G-CSF promoter activity. Further chromatin immunoprecipitation (ChIP) assays revealed that U0126 inhibits LPS-induced binding of NF-κB (p50/p65) and C/EBPβ to the G-CSF promoter, but not their nuclear protein levels. Knockdown of ERK2 inhibits LPS-induced accessibility of the G-CSF promoter region to DNase I, suggesting that chromatin remodeling may occur. These findings clarify that ERK2, rather than ERK1, mediates LPS-induced G-CSF expression in macrophages by remodeling chromatin, and stimulates C/ EBPβ-dependent activation of the G-CSF promoter. This study provides a potential target for regulating G-CSF expression.

Original languageEnglish
Article numbere0129685
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 26 2015

Fingerprint

granulocyte colony-stimulating factor
Macrophages
Granulocyte Colony-Stimulating Factor
lipopolysaccharides
Lipopolysaccharides
macrophages
promoter regions
Chromatin
chromatin
Chromatin Assembly and Disassembly
Assays
deoxyribonuclease I
protein secretion
Chromatin Immunoprecipitation
Deoxyribonuclease I
nuclear proteins
production economics
assays
Nuclear Proteins
small interfering RNA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chang, S. F., Lin, S. S., Yang, H. C., Chou, Y. Y., Gao, J. I., & Lu, S. C. (2015). LPS-induced G-CSF expression in macrophages is mediated by ERK2, but not ERK1. PLoS One, 10(6), [e0129685]. https://doi.org/10.1371/journal.pone.0129685

LPS-induced G-CSF expression in macrophages is mediated by ERK2, but not ERK1. / Chang, Shwu Fen; Lin, Shih Shan; Yang, Hui Ching; Chou, Yuan Yi; Gao, Jhen I.; Lu, Shao Chun.

In: PLoS One, Vol. 10, No. 6, e0129685, 26.06.2015.

Research output: Contribution to journalArticle

Chang, Shwu Fen ; Lin, Shih Shan ; Yang, Hui Ching ; Chou, Yuan Yi ; Gao, Jhen I. ; Lu, Shao Chun. / LPS-induced G-CSF expression in macrophages is mediated by ERK2, but not ERK1. In: PLoS One. 2015 ; Vol. 10, No. 6.
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