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

Irradiation increases the generation of reactive oxygen intermediates, including hydrogen peroxide (H2O2). Myeloperoxidase (MPO), a heme-containing glycoprotein located in the primary granules of polymorphonuclear leukocytes and monocytes, reacts with H2O2 and halide ion and produces a more potent microbicidal oxidant, hypochlorous acid (HOCI). 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 alpha (TNF alpha), and irradiation markedly increased the TNF alpha production in these cells; in turn, TNF alpha decreased the levels of MPO transcripts in these cells. Furthermore, treatment of cells with anti-TNF alpha 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 TNF alpha 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 TNF alpha is required for the reduction by irradiation in HL60 cells. (C) 2000 Elsevier Science B.V. All rights reserved.