Role of TNFalpha in regulation of myeloperoxidase expression in irradiated HL60 promyelocytic cells.
Irradiation increases the generation of reactive oxygen intermediates, including hydrogen peroxide (H(2)O(2)). Myeloperoxidase (MPO), a heme-containing glycoprotein located in the primary granules of polymorphonuclear leukocytes and monocytes, reacts with H(2)O(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 alpha (TNFalpha), and irradiation markedly increased the TNFalpha production in these cells; in turn, TNFalpha decreased the levels of MPO transcripts in these cells. Furthermore, treatment of cells with anti-TNFalpha 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 TNFalpha 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 TNFalpha is required for the reduction by irradiation in HL60 cells.
Hachiya
M
M
Division of Radiation Health, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba City, Japan.
Osawa
Y
Y
Akashi
M
M
D002454:Cell Differentiation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects*; D018922:HL-60 Cells; D006801:Humans; D009195:Peroxidase / Q000096:biosynthesis*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects; D015533:Transcriptional Activation / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase