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

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

Research output: Contribution to journalArticle

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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 Sedeficient 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.

Original languageEnglish (US)
Pages (from-to)1754-1761
Number of pages8
JournalJournal of Nutrition
Volume141
Issue number9
DOIs
StatePublished - Sep 1 2011

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Selenium
Interleukin-4
Macrophages
Arginase
Selenoproteins
Peroxisome Proliferator-Activated Receptors
Glutathione Peroxidase
Nitric Oxide Synthase
Anti-Inflammatory Agents
STAT6 Transcription Factor
Inflammation
Insurance Benefits
Interleukin-1
Knockout Mice
Wound Healing
Arginine
Diet
Phenotype

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

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title = "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 Sedeficient 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.",
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Selenium levels affect the IL-4-induced expression of alternative activation markers in murine macrophages. / Nelson, Shakira M.; Lei, Xingen; Prabhu, K. Sandeep.

In: Journal of Nutrition, Vol. 141, No. 9, 01.09.2011, p. 1754-1761.

Research output: Contribution to journalArticle

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T1 - Selenium levels affect the IL-4-induced expression of alternative activation markers in murine macrophages

AU - Nelson, Shakira M.

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AU - Prabhu, K. Sandeep

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