Inhibition of NF-κB by hydroquinone sensitizes human bone marrow progenitor cells to TNF-α-induced apoptosis

Suppression of hematopoiesis is an important mechanism governing blood cell formation. Factors such as tumor necrosis factor alpha (TNF-α) inhibit proliferation and colony-forming activity of bone marrow cells and activate nuclear factor kappa B (NF-κB) in multiple cell types. Activated NF-κB is required for many cells to escape apoptosis, including hematopoietic progenitor cells (HPC). The benzene metabolite hydroquinone (HQ) alters cytokine response and induces cell death in HPC, and inhibits NF-κB activation in T and B cells. Therefore, we studied the potential role of HQ-induced NF-κB inhibition in a hematopoietic cell line (TF-1) and primary HPC in rendering these cells susceptible to TNF-α-induced apoptosis. We demonstrate in both cell types that TNF-α activates NF-κB, and HQ exposure inhibits activation of NF-κB by TNF-α in a dose dependent manner. We further investigated the ability of HQ to potentiate TNF-α-induced apoptosis in these cells, and found that HQ sensitized the cells to the pro-apoptotic effect of TNF-α. These results suggest that NF-κB plays a key role in HPC survival, and that HQ-induced inhibition of NF-κB leaves these cells susceptible to cytokine-induced apoptosis. These effects may play a role in the suppression of hematopoiesis seen in some benzene exposed individuals.