Document Detail

Selenium levels affect the IL-4-induced expression of alternative activation markers in murine macrophages.
MedLine Citation:
PMID:  21775527     Owner:  NLM     Status:  MEDLINE    
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.
Shakira M Nelson; Xingen Lei; K Sandeep Prabhu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-07-20
Journal Detail:
Title:  The Journal of nutrition     Volume:  141     ISSN:  1541-6100     ISO Abbreviation:  J. Nutr.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-22     Completed Date:  2011-11-01     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1754-61     Citation Subset:  IM    
Graduate Program in Pathobiology, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA.
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MeSH Terms
Arginase / genetics,  metabolism
Biological Markers*
Cell Line
Cytokines / genetics,  metabolism*
Gene Expression
Glutathione Peroxidase / genetics,  metabolism
Inflammation / metabolism
Interleukin-4 / pharmacology*
Macrophage Activation / drug effects,  physiology*
Macrophages / drug effects*,  metabolism
Mice, Inbred C57BL
Selenium / blood*
Selenoproteins / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/Cytokines; 0/Selenoproteins; 207137-56-2/Interleukin-4; 7782-49-2/Selenium; EC 1.11.1.-/glutathione peroxidase GPX1; EC Peroxidase; EC protein, mouse; EC

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