Role of c-Jun in Tumor Necrosis Factor-alpha Inhibition of Activin A-mediated Erythroid Gene Expression in Erythroleukemia K562 Cells

Chih Wei Chen, Ming Hui Chung, Ju Ling Chang, Chin Wei Liu, Huei Mei Huang

Research output: Contribution to journalArticle

Abstract

Background: The activation of the tumor necrosis factor-alpha (TNF-α)/nuclear factor kappa B (NF-κB) pathway inhibits the expression of erythroid genes, whereas activin A, a member of the transforming growth factor-β superfamily, induces erythroid differentiation. The effect of TNF-α on activin A-induced erythroid gene expression has not been elucidated. Methods: Luciferase reporter assay and reverse transcription-polymerase chain reaction (PCR) or quantitative PCR were used to investigate globin promoter activity and globin gene expression in the hematopoietic progenitor cell line K562, respectively. Results: TNF-α inhibited the activin A-induced promoter activity of α-globin and ζ-globin in a concentration-dependent manner in K562 cells. Activin A could reverse the TNF-α-inhibited promoter activity of α-globin and ζ-globin in a concentration-dependent manner. TNF-α decreased the mRNA levels of α-globin, ζ-globin, GATA-1, and NF-E2 p45 induced by activin A. The NF-κB inhibitor, Bay117082, inhibited the TNF-α-increased c-Jun level. NF-κB p65 overexpression increased c-Jun protein and enhanced the TNF-α-increased c-Jun level. Furthermore, TNF-α inhibition of activin A-induced promoter activity and mRNA expression of α-globin and ζ-globin were abolished in cells expressing dominant-negative c-Jun. TNF-α inhibition of activin A-induced mRNA expression of GATA-1 and NF-E2 p45 was also abolished in cells expressing dominant-negative c-Jun. Conclusion: TNF-α may inhibit activin A-induced erythroid gene expression via increases of c-Jun in K562 cells.

Original languageEnglish
Pages (from-to)222-227
Number of pages6
JournalJournal of Experimental and Clinical Medicine(Taiwan)
Volume6
Issue number6
DOIs
Publication statusPublished - Dec 1 2014

Keywords

  • Activin A
  • C-Jun
  • Erythroid genes
  • K562 cells
  • TNF-α

ASJC Scopus subject areas

  • Medicine(all)

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