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

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
文章編號e0129685
期刊PLoS One
10
發行號6
DOIs
出版狀態已發佈 - 六月 26 2015

ASJC Scopus subject areas

  • 農業與生物科學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 醫藥 (全部)

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