摘要
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.
原文 | 英語 |
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頁(從 - 到) | 222-227 |
頁數 | 6 |
期刊 | Journal of Experimental and Clinical Medicine (Taiwan) |
卷 | 6 |
發行號 | 6 |
DOIs | |
出版狀態 | 已發佈 - 12月 1 2014 |
ASJC Scopus subject areas
- 一般醫學