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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Martitz, J. Becker, N-P Renko, K. Stoedter, M. Hybsier, S. Schomburg, L. |
| Description | Country affiliation: Germany Author Affiliation: Martitz J ( Institut für Experimentelle Endokrinologie, Charité- Universitätsmedizin Berlin, CVK, Südring 10, D-13353 Berlin, Germany. lutz.schomburg@charite.de.) |
| Abstract | 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 in severe sepsis. Selenium is incorporated into selenoproteins implicated in anti-oxidative defence, thyroid hormone metabolism and immunoregulation. Selenium metabolism is controlled by hepatocytes synthesizing and secreting the Se transporter selenoprotein P (SePP). The circulating SePP declines in sepsis causing low serum Se levels. Dysregulation of the hepatic selenoenzyme deiodinase type 1 (DIO1) potentially contributes to the low T3 (thyroid hormone) syndrome observed in severe diseases. We hypothesized that IL-6 affects hepatic selenoprotein biosynthesis directly. Testing human hepatocytes in culture, IL-6 reduced the concentrations of SePP mRNA and secreted SePP in a dose-dependent manner. In parallel, expression of DIO1 declined at the mRNA, protein and enzyme activity level. The effects of IL-6 on glutathione peroxidase (GPX) expression were isozyme-specific; GPX1 remained unaffected, while transcript concentrations of GPX2 increased and those of GPX4 decreased. This pattern of IL-6-dependent effects was mirrored in reporter gene experiments with SePP, DIO1, GPX1, and GPX2 promoter constructs pointing to direct transcriptional effects of IL-6. The redirection of hepatic selenoprotein biosynthesis by IL-6 may represent a central regulatory circuit responsible for the decline of serum Se and low T3 concentrations in sepsis. Accordingly, therapeutic IL-6 targeting may be effective for improving the Se and thyroid hormone status, adjuvant Se supplementation success and survival in sepsis. |
| File Format | HTM / HTML |
| ISSN | 17565901 |
| Issue Number | 11 |
| Volume Number | 7 |
| e-ISSN | 1756591X |
| Journal | Metallomics |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Publisher Date | 2015-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Interleukin-6 Metabolism Liver Selenium Selenoprotein P Glutathione Peroxidase Hep G2 Cells Hepatocytes Humans Genetics Sepsis Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics |
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