Role of TNFα in regulation of myeloperoxidase expression in irradiated HL60 promyelocytic cells

摘要

Irradiation increases the generation of reactive oxygen intermediates, including hydrogen peroxide (H_2O_2). Myeloperoxidase (MPO), a heme-containing glycoprotein located in the primary granules of polymorphonuclear leukocytes and monocytes, reacts with H_2O_2 and halide ion and produces a more potent microbicidal oxidant, hypochlorous acid (HOCl). Human HL60 promyelocytes constitutively had high levels of MPO protein and mRNA. Irradiation decreased the levels of MPO transcripts; the decrease in MPO transcripts by irradiation occurred in an almost dose-dependent manner. HL60 cells produce tumor necrosis factor α (TNFα), and irradiation markedly increased the TNFα production in these cells; in turn, TNFα decreased the levels of MPO transcripts in these cells. Furthermore, treatment of cells with anti-TNFα antibody blocked the reduction of MPO by irradiation. We also found that irradiation decreased the levels of the MPO mRNA with concomitant increased levels of TNFα mRNA in differentiation-induced HL60 cells and human THP-1 monocytic cells. Irradiation reduced the rate of MPO transcription but had only a slight effect on the half-life of MPO mRNA in HL60 cells. Our results suggest that irradiation reduces the steady-state levels of MPO mRNA mainly at transcriptional level and the endogenous production of TNFα is required for the reduction by irradiation in HL60 cells.