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

被引:18
作者
Buck, Isabelle [1 ]
Morceau, Franck [1 ]
Cristofanon, Silvia [1 ]
Reuter, Simone [1 ]
Dicato, Mario [1 ]
Diederich, Marc [1 ]
机构
[1] Hop Kirchberg, Lab Biol Mol & Cellulaire Canc, L-2540 Luxembourg, Luxembourg
关键词
tumor necrosis factor alpha; anemia; GATA-1/-2; Friend of GATA-1; inflammation; cancer; TUMOR-NECROSIS-FACTOR; FACTOR GATA-1; BONE-MARROW; CHROMATIN OCCUPANCY; CHRONIC DISEASE; MICE LACKING; FACTOR NF-E2; IFN-GAMMA; ANEMIA; CELLS;
D O I
10.3892/ijo_00000212
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 alpha (TNF alpha), 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 heroin (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 transctiptional activity and iv) inhibited erythroid marker gene expression (glycophorin A, erythropoietin receptor, gamma-globin) independently of the cell line or the inducer used. These data provided new insights into the role of GATA-1 regulation in TNF alpha-mediated inhibition of erythroid differentiation in erythroleukemia.
引用
收藏
页码:853 / 860
页数:8
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