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Up-Regulation of CD13/Aminopeptidase N Induced by Phorbol Ester Is Involved in Redox Regulation and Tumor Necrosis Factor α Production in HL-60 Cells

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Abstract

Here, we demonstrate the possible involvement of oxidative stress in altered CD13/aminopeptidase N (APN) expression during myeloid cell differentiation induced by TPA. In flow cytometrical analysis, CD13/APN protein was constitutively expressed in HL-60 cells. When the cells were treated with TPA, CD13/APN expression was up-regulated with increased intracellular peroxides and a morphological change into macrophage-like cells. This increase in CD13/APN expression was suppressed by treatment with N-acetylcysteine. Transfection of Mn-superoxide dismutase (MnSOD) gene to the cells also suppressed the up-regulated CD13/APN expression. Furthermore, a neutralizing antibody to TNFα partially blocked this up-regulation. These results indicate that the change in intracellular redox state could be involved in the up-regulation of CD13/APN expression during TPA-induced differentiation of HL-60 cells, suggesting that TNFα may serve as, at least, one of the signals stimulated by TPA.

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Hatanaka, Y., Ashida, H., Hashizume, K. et al. Up-Regulation of CD13/Aminopeptidase N Induced by Phorbol Ester Is Involved in Redox Regulation and Tumor Necrosis Factor α Production in HL-60 Cells. Inflammation 26, 175–181 (2002). https://doi.org/10.1023/A:1016567729182

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