Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans

Abstract

Background Selenium and peroxynitrite are known to support the growth and activity of immune cells, including T cells, B cells and macrophages. However, the role of these factors in the immune function of human immature dendritic cells (imDCs) is not clear. Material/Methods Monocytes from a mixture of blood samples were isolated using Ficoll density gradient centrifugation and purified with immunomagnetic beads before being induced into imDCs. Cells then either received no treatment (control group), or treatment with sodium selenite (Na 2 SeO 3 , Se), 3-morpholinosydnonimine (SIN1, which decomposes into peroxynitrite), or Se+SIN1. Cell viability, migration, and antiphagocytic abilities, oxidative stress, and protein expression of extracellular signal-regulated kinases (ERK) and MMP2 were assessed using a CCK8 assay, cell counter and flow cytometry, microplate spectrophotometer, and Western blot analysis, respectively. Results Viability of imDCs was unaffected by 0.1 μmol/L of Na 2 SeO 3 , although 1 mmol/L of SIN1 decreased it significantly ( P <0.05). Chemotactic migration and antiphagocytic abilities were inhibited and enhanced, respectively, by treatment with Na 2 SeO 3 and SIN1 ( P <0.05). Activities of superoxide dismutase and glutathione peroxidase were increased by Na 2 SeO 3 and Se+SIN1 ( P <0.001). Glutathione content decreased with exposure to Na 2 SeO 3 and SIN1 ( P <0.05), but increased after treatment with Se+SIN1 ( P <0.05). Levels of reactive oxygen species only increased with SIN1 treatment ( P <0.05). Treatment with Na 2 SeO 3 , SIN1 and Se+SIN1 increased ERK phosphorylation and decreased MMP2 protein expression ( P <0.05). Conclusions Selenium and peroxynitrite can influence immune function in imDCs by regulating levels of reactive oxygen species or glutathione to activate ERK and promote antigen phagocytosis, as well as by decreasing MMP2 expression to inhibit chemotactic migration.

Selenium stimulates the antitumour immunity: Insights to future research

“…In vitro study showed that Se could influence immune function by enhancing the levels of ROS or glutathione, which subsequently activate extracellular signal-regulated kinases (ERK) and promoting antigen phagocytosis in immature dendritic cells (DCs). Furthermore, the expression of matrix metalloproteinases is decreased to inhibit chemotactic migration [42]. However, the effect of Se on ROS scavengers is dependent on the Se exposure level.…”

Selenoprotein K Is Essential for the Migration and Phagocytosis of Immature Dendritic Cells

“…Several previous studies have demonstrated that the immune function of chicken DCs was regulated by selenium [ 2 , 3 ]. Our recent studies have also illustrated that selenium can regulate the differentiation and maturation of human DCs [ 4 , 5 ], and its deficiency and excess impaired the DCs’ immune function [ 6 ] and reduced the number of splenic DCs in mice [ 7 ]. It is well known that selenium exerts its biological effect through selenoprotein, and the effect of selenium on the DCs’ immune function in chickens [ 2 , 3 ], humans [ 5 ] and mice [ 6 , 7 ] was related to changes in the levels of selenoprotein.…”

Advances in the Study of the Mechanism by Which Selenium and Selenoproteins Boost Immunity to Prevent Food Allergies

“…Previous studies have shown that Se can regulate mouse helper T-cell (Th) differentiation, antibody production, leukocyte adhesion and migration, and macrophage phagocytosis [ 4 , 21 ]. Recent studies have confirmed that Se can regulate the immune response of DCs in chickens, mice, and humans [ 49 , 65 , 66 , 67 ]. Potential mechanisms by which Se is involved in the regulation of immune cell function include reactive oxygen species production and species, calcium and redox signaling, extracellular signal-regulated kinase (ERK), hypoxia-inducible factor 1α (HIF-1α), and NF-κB pathways [ 67 , 68 , 69 , 70 , 71 , 72 ].…”