Selenium modifies inflammatory reactions in rodents and humans. The liver controls metabolism and transport of selenium via hepatically-derived SEPP (selenoprotein P). Intracellular SEPS (selenoprotein S) modifies endoplasmic-reticulum function and immune-cell activity. Polymorphisms in SEPS have been associated with cytokine levels and inflammatory diseases in a subset of clinical studies. In the present study, we hypothesized that sex and selenium represent decisive parameters controlling the immune response and regulation of SEPS expression in vivo. Male and female mice fed a selenium-poor diet were supplemented or not with selenite for 3 days and injected with saline or LPS (lipopolysaccharide) 24 h before analysis. Selenium supplementation mitigated the LPS-induced rise in circulating cytokines in male mice. Serum SepP and selenium concentrations decreased in response to LPS, whereas hepatic SepS was specifically up-regulated despite declining selenium concentrations in the liver. Hepatic SepS induction was mainly controlled by post-transcriptional mechanisms and attributed to hepatocytes by analysing transgenic mice. Notably, selenium supplementation was essential for an optimal SepS induction. We conclude that selenoprotein biosynthesis becomes redirected in hepatocytes during the acute-phase response at the expense of dispensable selenoproteins (e.g. SepP) and in favour of SepS expression, thereby causing declining serum selenium and improving liver function. The selenium status and sex control SepS expression and modify cytokine response patterns in serum, which might explain contradictory results on associations of SEPS genotype and inflammatory diseases in clinical studies.
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Research Article|
June 14 2010
Selenium controls the sex-specific immune response and selenoprotein expression during the acute-phase response in mice
Mette Stoedter;
Mette Stoedter
1
1Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Südring 10, D-13353 Berlin, Germany
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Kostja Renko;
Kostja Renko
1
1Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Südring 10, D-13353 Berlin, Germany
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Antonia Hög;
Antonia Hög
1Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Südring 10, D-13353 Berlin, Germany
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Lutz Schomburg
Lutz Schomburg
2
1Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Südring 10, D-13353 Berlin, Germany
2To whom correspondence should be addressed (email lutz.schomburg@charite.de).
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Publisher: Portland Press Ltd
Received:
December 09 2009
Revision Received:
March 18 2010
Accepted:
April 06 2010
Accepted Manuscript online:
April 06 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 429 (1): 43–51.
Article history
Received:
December 09 2009
Revision Received:
March 18 2010
Accepted:
April 06 2010
Accepted Manuscript online:
April 06 2010
Citation
Mette Stoedter, Kostja Renko, Antonia Hög, Lutz Schomburg; Selenium controls the sex-specific immune response and selenoprotein expression during the acute-phase response in mice. Biochem J 1 July 2010; 429 (1): 43–51. doi: https://doi.org/10.1042/BJ20091868
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