Abstract
Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping the immunoregulatory cytokine and lipid mediator profile. How exactly differentiation of monocytes into macrophages influences the expression of the selenoproteome in concert with the Se supply remains obscure. THP-1 monocytes were differentiated with phorbol 12-myristate 13-acetate (PMA) into macrophages and (i) the expression of selenoproteins, (ii) differentiation markers, (iii) the activity of NF-κB and NRF2, as well as (iv) lipid mediator profiles were analyzed. Se and differentiation affected the expression of selenoproteins in a heterogeneous manner. GPX4 expression was substantially decreased during differentiation, whereas GPX1 was not affected. Moreover, Se increased the expression of selenoproteins H and F, which was further enhanced by differentiation for selenoprotein F and diminished for selenoprotein H. Notably, LPS-induced expression of NF-κB target genes was facilitated by Se, as was the release of COX- and LOX-derived lipid mediators and substrates required for lipid mediator biosynthesis. This included TXB2, TXB3, 15-HETE, and 12-HEPE, as well as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Our results indicate that Se enables macrophages to accurately adjust redox-dependent signaling and thereby modulate downstream lipid mediator profiles.
Highlights
Selenium (Se) is an essential trace element that is important for human health
To investigate the effect of Se on the differentiation process of human THP-1 leukemic monocytes into macrophages, we initially determined the Se concentration and incubation time required for adequate expression of Se-sensitive selenoproteins
Concentrationdependent studies with 0–500 nM sodium selenite for 72 h confirmed a significant upregulation of the protein expression levels of the Se-sensitive selenoproteins GPX1 and SELENOH (Figure S1a,b), while expression of TXNRD1 was not affected (Figure S1c)
Summary
Selenium (Se) is an essential trace element that is important for human health. It is required for various physiological processes including immune function and mammalian development, as well as thyroid hormone metabolism, and Se deficiency has been implicated in various pathologies including inflammation, heart disease, and cancer [1,2]. Expression levels of selenoproteins largely differ between undifferentiated and differentiated cells, which suggests that distinct selenoproteins inherit specific functions depending on the differentiation state. Various other selenoproteins, such as glutathione peroxidases (GPXs), SELENOO, and SELENOK, have been shown to be implicated in proliferation and differentiation of distinct cell types [4,8,9]
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