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Selenoprotein induced M1 to M2 murine macrophage phenotype switching is imperative in helminth parasite clearance
Author(s) -
Nelson Shakira M,
Carlson Bradley,
Urban Joseph,
Lei Xingen,
Hatfield Dolph,
Prabhu K. Sandeep
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.253.6
Subject(s) - selenoprotein , macrophage , interleukin 4 , biology , nippostrongylus brasiliensis , microbiology and biotechnology , phenotype , m2 macrophage , immunology , chemistry , immune system , in vitro , biochemistry , enzyme , glutathione peroxidase , superoxide dismutase , gene
Selenium (Se) in the form of selenoproteins, imparts many beneficial health and anti‐inflammatory properties. In the present study, we investigated the anti‐inflammatory activity of Se using a LPS and IL4 treated murine BMDM model. IL4‐treated macrophages supplemented with 100 nM Se 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 cultured in 100 nM Se and IL4, suggesting a synergistic effect of Se and IL4. Additional studies utilizing tRNA [Ser]Sec (Trsp) KO mice macrophages, characterized by a total loss of selenoprotein expression, showed a complete abrogation of Arg‐I activity, even under high Se (250nM) conditions, demonstrating the importance of selenoproteins. Current in vivo studies, using the helminthic parasite Nippostrongylus brasiliensis , show a significant increase in intestinal M2 marker expression, in addition to a decreased presence of intestinal adult worms and fecal eggs, in Se supplemented mice. These data suggest that optimal selenium status, in the form of selenoproteins, is critical to skew macrophage activation to promote resolution of (parasite) infection. NIH grant DK077152.