The Effect of Selenoproteins on Infection-Mediated Inflammation and Gut Epithelial Barrier Integrity
Open Access
- Author:
- Herold, Morgan
- Area of Honors:
- Immunology and Infectious Disease
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. Kumble Sandeep Prabhu, Thesis Supervisor
Dr. Pamela A. Hankey-Giblin, Thesis Honors Advisor - Keywords:
- selenium
inflammation
gut
gut barrier integrity
citrobacter rodentium
tight junction protein
immunology
cox
cytokines - Abstract:
- Inflammation has been proven to play a key role in both the resolution of gut bacterial infections and the translocation of such bacteria to neighboring organs. It is thus to be expected that, by limiting the production of pro-inflammatory cytokines such as TNF-α and IL-1, resolution of infection will be maximized while dissemination of bacteria across the gut epithelial barrier will be minimized. Selenium, an essential micronutrient obtained via dietary sodium selenite and incorporated into selenoproteins, is known to interfere with the COX pathway upstream of such cytokines via PPARγ mediated inhibition of NF-kB. In order to elucidate the definitive effects of selenium on inflammatory responses to bacterial infection, mice were fed diets either deficient or supplemented with selenium and then infected with Citrobacter rodentium. Mice from each diet group were dissected via IACUC protocols at both 9 and 16 days p.i., and portions of the colon were allocated for both mRNA and protein isolation. In addition to measurements of cytokines in the colon related to the inflammatory pathway, bacterial dissemination to the liver and spleen and quantities of epithelial barrier tight junction protein were also measured. Via both qRT-PCR and Western Blot techniques to measure mRNA and protein expression respectively, it was determined that mice fed a Se-supplemented diet recovered faster from infection, produced fewer pro-inflammatory cytokines, had mildly lessened translocation of bacteria to neighboring organs, and produced more epithelial barrier proteins. Based on this study, it is suggested that a diet supplemented with selenium may benefit the gut in response to inflammation. In addition, the increased integrity of the gut epithelial barrier in Se-supplemented conditions suggests that dietary sodium selenite may be a way to prevent bacterial translocation.