Gene-specific regulation of hepatic selenoprotein expression by interleukin-6

摘要: Sepsis is a severe inflammatory disease resulting in excessive production of pro-inflammatory cytokines including interleukin-6 (IL-6), causing oxidative stress, tissue damage and organ dysfunction. Health benefits have been observed upon selenium (Se) supplementation sepsis. Selenium incorporated into selenoproteins implicated anti-oxidative defence, thyroid hormone metabolism immunoregulation. controlled by hepatocytes synthesizing secreting the Se transporter selenoprotein P (SePP). The circulating SePP declines sepsis low serum levels. Dysregulation hepatic selenoenzyme deiodinase type 1 (DIO1) potentially contributes to T3 (thyroid hormone) syndrome diseases. We hypothesized that IL-6 affects biosynthesis directly. Testing human culture, reduced concentrations mRNA secreted dose-dependent manner. In parallel, expression DIO1 declined at mRNA, protein enzyme activity level. effects on glutathione peroxidase (GPX) were isozyme-specific; GPX1 remained unaffected, while transcript GPX2 increased those GPX4 decreased. This pattern IL-6-dependent was mirrored reporter gene experiments with SePP, DIO1, GPX1, promoter constructs pointing direct transcriptional IL-6. redirection may represent central regulatory circuit responsible for decline Accordingly, therapeutic targeting be effective improving status, adjuvant success survival