Premium
Regulation of arginase‐I expression in macrophages by selenium
Author(s) -
Nelson Shakira M,
Gandhi Ujjawal H,
Kaushal Naveen,
Prabhu K. Sandeep
Publication year - 2010
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.24.1_supplement.894.6
Subject(s) - arginase , chemistry , lipopolysaccharide , macrophage , inflammation , nitric oxide , ornithine , nitric oxide synthase , enzyme , cytokine , biochemistry , arginine , microbiology and biotechnology , biology , immunology , amino acid , organic chemistry , in vitro
Selenium (Se) is an essential micronutrient with anti‐inflammatory properties. It has been previously shown that Se supplementation of macrophages led to a decrease in bacterial endotoxin lipopolysaccharide (LPS)‐induced expression of inducible nitric oxide synthase (iNOS), a prototypical marker of classical (M1) macrophage activation. We believe that L‐arginine, a substrate for iNOS, is now acted upon by arginase‐1 (Arg‐1), a marker of alternate (M2) activation. Arg‐1 produces L‐ornithine, which serves as a precursor for the synthesis of collagen and polyamines that are essential components of catabasis or wound healing responses. Using murine bone marrow‐derived macrophages and RAW 264.7 cell models, we have examined Se effects on Arg‐1 transcription, protein expression, and enzyme activity. Following IL‐4 treatment, an alternative activation cytokine, the Arg‐1 mRNA, protein and enzyme activity were significantly increased in Se supplemented macrophages when compared to Se deficient counterparts. Stimulation of these cells with LPS caused a further increase in Arg‐1 expression suggesting a synergistic effect of Se and IL‐4 on Arg‐1 expression even under inflammatory conditions. These data show that optimal Se status is critical for alternative macrophage activation, leading to attenuated inflammation. National Institute of Health grant DK077152.