• Journal of Life Science
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• v.34 no.4
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• pp.271-278
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• 2024

Redox factor (Ref)-1, a ubiquitously expressed protein, acts as a modulator of redox-sensitive tran- scription factors and as an endonuclease in the repair pathway of damaged DNA. However, the function of Ref-1 in the differentiation of monocytes into macrophages has not been defined. In this study, we investigated the effects of Ref-1 on the monocyte differentiation process using the human monocytic cell line THP-1. The differentiation agent PMA increased cell adhesion over time and showed a sig- nificant increase in phagocytic function but decreased the intracellular amount of Ref-1. Ref-1 inhibitor E3330 and Ref-1 knockdown using the siRNA technique reduced cell adhesion and the expression of differentiation markers, such as CD14, ICAM-1, and CD11b, by PMA stimulation. This means that the role of Ref-1 is absolutely necessary in the initial process of differentiating THP-1 cells stimulated by PMA. Next, the distribution of Ref-1 was examined in the cytoplasm and nucleus of THP-1 cells stimulated with PMA. Surprisingly, PMA stimulation resulted in the rapid translocation of Ref-1 to the nucleus. To prove that movement of Ref-1 to the nucleus is required for monocyte differentiation, a Ref-1 vector with the nuclear localization sequence (NLS) deleted was used. As a result, overexpression of ∆NLS Ref-1, which restricted movement to the nucleus, suppressed the expression of differentiation markers and notably reduced phagocytic function in PMA-stimulated THP-1 cells. In conclusion, these data suggest that the differentiation of monocytic THP-1 cells requires Ref-1 nuclear translocation during the initial process of biochemical events following stimulation from PMA.