Selenium levels are critical for the IL‐4 induced expression of alternative activation markers in murine macrophages

Selenium (Se) in the form of selenoproteins, imparts many health benefits and anti‐inflammatory properties. In the present study, we investigated the anti‐inflammatory activity of Se using a LPS and IL4 treated murine bone marrow‐derived macrophage model. Supplementation with Se (100 nM) of IL4 treated macrophages significantly increased the expression of alternatively activated macrophage (M2) markers, Arg‐I and Mrc‐1. Se treatment also increased the enzymatic activity of Arg‐I and surface expression of Mrc‐1. Conversely, expression of classically activated macrophage (M1) markers, TNFα, and IL1β, were significantly decreased in LPS treated macrophages that were cultured in 100 nM Se and IL4, suggesting a synergistic effect of Se and IL4. Furthermore, studies with inhibitors of two transcription factors, PPARγ and STAT6, which are pivotal for the activity of Se and IL4, respectively, completely ablated the Se dependent expression of M2 markers. Similar results were also obtained with pharmacological inhibitors of hematopoietic prostaglandin D 2 synthase enzymes, suggesting Se supplementation of macrophages produces endogenous activators from the arachidonic acid pathway to mediate PPARγ‐dependent switch from M1 to M2 phenotype in the presence of IL4. These data show that optimal selenium status is critical to affect macrophage activation and resolution of inflammation. NIH grant DK077152