Differential expression of glutaredoxin and thioredoxin during monocytic differentiation

Abstract Macrophages generate reactive oxygen intermediates (ROIs) as the effectors of anti-bacterial defense mechanism. Intracellular ROIs and reduction/oxidation (redox) status play crucial roles in signal transduction. We therefore investigated the expression of redox-regulating proteins such as glutaredoxin (GRX) and thioredoxin (TRX) during the differentiation of murine monocytic leukemia cell line M1 cells and human monocytic leukemia cell line U937 cells. When M1 cells were treated by IL-6, GRX mRNA markedly increased and TRX mRNA also increased slightly. In contrast, there was no increase of GRX mRNA in D-cell, which is a sub-cell line derived from M1 lacking in the capacity of differentiation. GRX mRNA also increased in U937 cells differentiated by phorbol 12-myristate 13-acetate (PMA). By immunohistochemistry, unstimulated M1 cells showed strong staining of TRX and marginal staining of GRX. In contrast, TRX expression in IL-6 treated M1 cells is as strong as in unstimulated M1 cells, whereas GRX expression is slightly enhanced in IL-6 treated M1 cells. Phagocytosis is markedly enhanced and hydrogen peroxide production is slightly enhanced in IL-6 treated M1 cells. These results showed that TRX is steadily expressed whereas GRX is induced in association with the differentiation in macrophage-like cell line cells, suggesting differential roles of these redox regulators in macrophage lineage.