Selenium levels affect the IL-4-induced expression of alternative activation markers in murine macrophages.

Abstract

Selenium (Se), in the form of selenoproteins, imparts many health benefits with antiinflammatory properties. Previous studies have shown that Se supplementation of macrophages negatively regulates the LPS-dependent production of inducible NO synthase (iNOS), a proinflammatory gene. Therefore, we hypothesized that l-arginine, a substrate for iNOS, is acted upon by arginase-I (Arg-I), contributing to the resolution of inflammation. We investigated the antiinflammatory activity of Se using LPS and IL-4-treated C57BL/6 murine bone marrow-derived macrophages (BMDM) from mice fed Se-deficient and Se-adequate diets. Supplementation with Se (100 nmol/L) of IL-4-treated macrophages significantly increased the expression of alternatively activated macrophage (M2) markers, Arg-I, Fizz1, 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 IL-1β, was significantly decreased in LPS-treated macrophages that were cultured in Se and IL-4, suggesting a synergistic effect between Se and IL-4. Additionally, Arg-I activity was decreased in BMDM harvested from glutathione peroxidase (GPX) knockout mice compared to GPX wild-type mice, further establishing an important role for selenoproteins. Furthermore, BMDM treated with inhibitors of PPARγ and STAT6, pivotal transcription factors that mediate the activity of Se and IL-4, respectively, showed complete ablation of Se-dependent expression of M2 markers. In summary, these studies suggest that Se supplementation of macrophages produces endogenous activators to mediate the PPARγ-dependent switch from M1 to M2 phenotype in the presence of IL-4, possibly affecting pathways of wound healing and inflammation resolution.

• Authors: Shakira M Nelson, Xingen Lei, K Sandeep Prabhu
• Journal: The Journal of nutrition (J Nutr) Vol. 141 Issue 9 Pg. 1754-61 (Sep 2011) ISSN: 1541-6100 [Electronic] United States
• PMID: 21775527 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers
• Cytokines
• Selenoproteins
• Interleukin-4
• Glutathione Peroxidase
• Arg1 protein, mouse
• Arginase
• Selenium
• Glutathione Peroxidase GPX1
• Gpx1 protein, mouse

Topics

• Animals
• Arginase (genetics, metabolism)
• Biomarkers
• Cell Line
• Cytokines (genetics, metabolism)
• Diet
• Gene Expression
• Glutathione Peroxidase (genetics, metabolism)
• Inflammation (metabolism)
• Interleukin-4 (pharmacology)
• Macrophage Activation (drug effects, physiology)
• Macrophages (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Selenium (blood)
• Selenoproteins (genetics, metabolism)
• Glutathione Peroxidase GPX1