Selenium controls sex-specific immune response and selenoprotein expression during the acute phase response in mice

Mette Stoedter , Kostja Renko , Antonia Hoeg , Lutz Schomburg (1)

1 Experimental Endocrinology

Selenium modifies inflammatory reactions in rodents and humans. The liver controls metabolism and transport of selenium via hepatically-derived selenoprotein P (SEPP). Intracellular selenoprotein S (SEPS) modifies endoplasmic reticulum function and immune cell activity. Polymorphisms in SEPS were associated with cytokine levels and inflammatory diseases in a subset of clinical studies. We hypothesized that sex and selenium represent decisive parameters controlling immune response and regulation of SEPS expression in vivo. Male and female mice on Se-poor diet were supplemented or not with selenite for three days and injected with saline or LPS 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 Se concentrations in liver. Hepatic SepS induction was mainly controlled by posttranscriptional 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. 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.

Mots clés: Life Sciences

Mette Stoedter, Kostja Renko, Antonia Hoeg, Lutz Schomburg. Selenium controls sex-specific immune response and selenoprotein expression during the acute phase response in mice. Biochemical Journal, 2010, 429 (1), pp.43-51. ⟨10.1042/BJ20091868⟩. ⟨hal-00491630⟩