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The inhibitory effect of the proinflammatory cytokine TNFα on erythroid differentiation involves erythroid transcription factor modulation

Authors
Type
Published Article
Journal
International Journal of Oncology
Publisher
Spandidos Publications
Publication Date
Feb 09, 2009
Volume
34
Issue
3
Identifiers
DOI: 10.3892/ijo_00000212
Source
LBMCC
License
White

Abstract

The hematopoietic transcription factor GATA-1 regulates the expression of several genes associated with differentiation of erythroid cells. We show here the inhibitory effect of tumor necrosis factor α (TNFα), a proinflammatory cytokine, on hemoglobinization and erythroid transcription factor GATA-1 expression in erythroleukemia (HEL) as well as in chronic myelogenous leukemia (K562) cells, which were induced to differentiate towards the erythroid lineage after aclacinomycin (Acla), doxorubicin (Dox) or hemin (HM) treatment. As a result, we observed i) a decreased expression of Friend of GATA-1 (FOG-1), an essential cofactor of GATA-1 transcription factor, ii) a downregulation of GATA-1 by proteasomal degradation and iii) a reduced acetylation level of GATA-1 in HM-induced K562 cells after TNF treatment. As a result, these modifications i) decreased the level of GATA-1/FOG-1 complex, ii) unsettled the GATA-1/GATA-2 balance, iii) reduced GATA-1 transcriptional activity and iv) inhibited erythroid marker gene expression (glycophorin A, erythropoietin receptor, γ-globin) independently of the cell line or the inducer used. These data provided new insights into the role of GATA-1 regulation in TNFα-mediated inhibition of erythroid differentiation in erythroleukemia.

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