Selenium Levels Affect the IL-4–Induced Expression of Alternative Activation Markers in Murine Macrophages  

Oleh:

Nelson, Shakira M. ; Lei, Xingen ; Prabhu, K. Sandeep

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 141 no. 09 (Sep. 2011), page 1754-1761 .
Topik: NUTRITIONAL IMMUNOLOGY

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2011.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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, TNFa, and IL-1ß, 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 PPAR? 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 PPAR?-dependent switch from M1 to M2 phenotype in the presence of IL-4, possibly affecting pathways of wound healing and inflammation resolution.

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