Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic Differentiation through Nuclear Factor-κB-Related Survival Pathway Down-Regulation

Por um escritor misterioso
Last updated 26 março 2025
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Arsenic trioxide (As2O3) is known to be toxic toward leukemia cells. In this study, we determined its effects on survival of human monocytic cells during macrophagic differentiation, an important biological process involved in the immune response. As2O3 used at clinically relevant pharmacological concentrations induced marked apoptosis of human blood monocytes during differentiation with either granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor. Apoptosis of monocytes was associated with increased caspase activities and decreased DNA binding of p65 nuclear factor-κB (NF-κB); like As2O3, the selective NF-κB inhibitor ( E )-3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (Bay 11-7082) strongly reduced survival of differentiating monocytes. The role of NF-κB in arsenic toxicity was also studied in promonocytic U937 cells during phorbol 12-myristate 13-acetate-induced macrophagic differentiation. In these cells, As2O3 first reduced DNA binding of p65 NF-κB and subsequently induced apoptosis. In addition, overexpression of the p65 NF-κB subunit, following stable infection with a p65 retroviral expressing vector, increased survival of As2O3-treated U937 cells. As2O3 specifically decreased protein levels of X-linked inhibitor of apoptosis protein and FLICE-inhibitory protein, two NF-κB-regulated genes in both U937 cells and blood monocytes during their differentiations. Finally, As2O3 was found to inhibit macrophagic differentiation of monocytic cells when used at cytotoxic concentrations; however, overexpression of the p65 NF-κB subunit in U937 cells reduced its effects toward differentiation. In contrast to monocytes, well differentiated macrophages were resistant to low concentrations of As2O3. Altogether, our study demonstrates that clinically relevant concentrations of As2O3 induced marked apoptosis of monocytic cells during in vitro macrophagic differentiation likely through inhibition of NF-κB-related survival pathways.
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Frontiers The diverse roles of macrophages in metabolic inflammation and its resolution
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Pathogens, Free Full-Text
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Frontiers The generation, activation, and polarization of monocyte-derived macrophages in human malignancies
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Cells, Free Full-Text
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic Differentiation through Nuclear Factor-κB-Related Survival Pathway Down- Regulation
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Macrophage Reprogramming via Targeted ROS Scavenging and COX-2 Downregulation for Alleviating Inflammation
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Cancers, Free Full-Text
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
IJMS, Free Full-Text
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic  Differentiation through Nuclear Factor-κB-Related Survival Pathway  Down-Regulation
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic Differentiation through Nuclear Factor-κB-Related Survival Pathway Down- Regulation

© 2014-2025 startwindsor.com. All rights reserved.