Potential Role of the 15kDa Selenoprotein in Colorectal Inflammation

Abstract

The micronutrient selenium (Se) exerts its mechanistic effects largely through incorporation into selenoproteins. The 15kDa selenoprotein (Sep15) is thought to be involved in regulation of protein folding, as well as in cell homeostasis as an oxidoreductase. Previous results suggest that Sep15 deficiency is protective against formation of pre‐neoplastic lesions in colon epithelia, possibly due to increased interferon‐γ‐regulated gene expression, suggesting a role for Sep15 in inflammation. Currently, we are examining Sep15 knockout (KO) mice and littermate controls that were maintained on Se‐deficient (0.02 ppm) or Se‐adequate (0.1 ppm) diets, as Se‐deficiency itself results in upregulation of inflammation‐associated gene expression. Treatment with 2% dextran sulfate sodium (DSS) in drinking water for one week was used to induce colitis. To examine the role of Sep15 and dietary Se in inflammation, serum and spleens were collected, and mRNA and protein were isolated from colon epithelial tissues and spleens. Gene expression is being analyzed by microarray analyses, quantitative RT‐PCR, ELISA and Western blotting. Preliminary results show that serum interleukin‐6 levels were increased in Sep15 KO mice compared to controls, independent of Se and DSS treatment. In contrast, serum interferon‐γ was significantly higher in Sep15 KO mice compared to littermate controls under Se‐deficient conditions, but decreased under Se‐adequate conditions. The contribution of other cytokines is currently being assessed. Microarray analyses of colon epithelia showed that mRNA expression of the seven top up‐regulated genes in Sep15 KO mice were changed regardless of DSS treatment. These genes are known to be involved in immune and pro‐inflammatory responses. Inflammation‐related gene expression in spleens is currently being assessed; however, spleen mass as percent of body weight did not change significantly between control and Sep15 KO mice, dietary Se, or DSS treatment. Thus, our preliminary analyses indicate that Sep15 may influence the expression of and changes in pro‐inflammatory genes, and that Sep15 may be involved in the regulation of inflammatory responses.Support or Funding InformationNCI Intramural support; NIH CA080946 (VNG); Office of Dietary Supplements; Towson University Jess & Mildred Fisher Endowed Chair (PAT)