Decreased selenoprotein expression alters the immune response during influenza virus infection in mice.
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Sheridan PA, Zhong N, Carlson BA, Perella CM, Hatfield DL, Beck MA
Decreased selenoprotein expression alters the immune response during influenza virus infection in mice.
J Nutr. 2007 Jun;137(6):1466-71.
- PubMed ID
- 17513408 [ View in PubMed]
- Abstract
Previous work from our laboratory demonstrated that host selenium (Se) deficiency results in greater lung pathology and altered immune function in mice infected with influenza virus. Because selenoproteins play a key role in determining the oxidant status of the host, we utilized a transgenic mouse line carrying a mutant selenocysteine (Sec) tRNA ([Ser]Sec) transgene (t-trspi(6)A(-)). The levels of selenoproteins are decreased in these mice in a protein- and tissue-specific manner. Male t-trspi(6)A(-) and wild-type (WT) mice were infected with influenza and killed at various time points postinfection (p.i.). Lung mRNA levels for innate and pro-inflammatory cytokines increased with infection but did not differ between groups. However, at d 2 p.i., chemokine levels were greater in the t-trspi(6)A(-) mice compared with WT mice. Additionally, IFN-gamma was higher at d 7 p.i. in the t-trspi(6)A(-) mice and viral clearance slower. Despite these immune system changes, lung pathology was similar in t-trspi(6)A(-) and WT mice. (75)Se labeling experiments demonstrated that glutathione peroxidase (GPX)-1 and thioredoxin reductase, although greatly diminished in the lungs of t-trspi(6)A(-) mice, were not altered as a result of infection. GPX-1 activity in the lungs of the t-trspi(6)A(-) mice was approximately 82% of the WT mice. In addition, the GPX-1 activity in the lungs of Se-deficient mice was 125% less than in the t-trspi(6)A(-) mice. These results suggest that although selenoproteins are important for immune function, there is a threshold of GPX-1 activity that can prevent an increase in lung pathology during influenza infection.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Glutathione Glutathione peroxidase Protein Humans UnknownNot Available Details