title: Selenium and inflammatory bowel disease.
abstract: Dietary intake of the micronutrient selenium is essential for normal immune functions. Selenium is cotranslationally incorporated as the 21st amino acid, selenocysteine, into selenoproteins that function to modulate pathways involved in inflammation. Epidemiological studies have suggested an inverse association between selenium levels and inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis that can potentially progress to colon cancer. However, the underlying mechanisms are not well understood. Here we summarize the current literature on the pathophysiology of IBD, which is multifactorial in origin with unknown etiology. We have focused on a few selenoproteins that mediate gastrointestinal inflammation and activate the host immune response, wherein macrophages play a pivotal role. Changes in cellular oxidative state coupled with altered expression of selenoproteins in macrophages drive the switch from a proinflammatory phenotype to an anti-inflammatory phenotype to efficiently resolve inflammation in the gut and restore epithelial barrier integrity. Such a phenotypic plasticity is accompanied by changes in cytokines, chemokines, and bioactive metabolites, including eicosanoids that not only mitigate inflammation but also partake in restoring gut homeostasis through diverse pathways involving differential regulation of transcription factors such as nuclear factor-κB and peroxisome proliferator-activated receptor-γ. The role of the intestinal microbiome in modulating inflammation and aiding in selenium-dependent resolution of gut injury is highlighted to provide novel insights into the beneficial effects of selenium in IBD.
authors.affiliation: Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Avinash K
authors.initials: AK
authors.lastname: Kudva
authors.affiliation: Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Shay
authors.affiliation: Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania ksprabhu@psu.edu.
authors.forename: K Sandeep
authors.initials: KS
authors.lastname: Prabhu
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism; D004032:Diet; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D064307:Microbiota; D010084:Oxidation-Reduction; D012307:Risk Factors; D012643:Selenium / Q000276:immunology / Q000378:metabolism*; D051140:Selenoproteins / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D051140:Selenoproteins; D012643:Selenium
keywords: cyclooxygenase; glutathione peroxidase; prostaglandin; selenoproteins