Inflammatory diseases are characterized by uncontrolled inflammation and remain the leading cause of death in humans. Selenium (Se) is an essential nutrient in the mammalian diet and its bioactivities are critical for optimum immune function. Se exhibits immune-modulatory effects through antioxidant-functioning selenoproteins that can exert control over oxidative tone of cells and the expression of pro-inflammatory mediators. Oxylipids are among the more potent, redox-regulated inflammatory mediators that orchestrate the degree and duration of inflammation. Whereas previous works show Se-deficiency results in enhanced pro-inflammatory, arachidonic acid-derived oxylipid synthesis by macrophages, there is a need to define how antioxidant selenoprotein activity might control the balance between pro- and anti-inflammatory oxylipid biosynthesis. Therefore the objective of this work was to investigate the role of decreased selenoprotein activity in modulating the production of biologically active oxylipids from macrophages. Reduced selenoprotein activity increased free radicals, enhanced inflammatory cytokine expression, and decreased LA-derived oxylipids from both in vivo and in vitro macrophages. When these oxylipids were added to in vitro macrophages subjected to a pro-oxidant challenge, inflammatory TNF-alpha; production was abrogated, suggesting an anti-inflammatory action for these LA-derived oxylipids. Future studies should focus on which antioxidant selenoproteins have an impact on oxylipid biosynthesis and the mechanisms behind their effect in order to help prevent pathologies associated with uncontrolled inflammation.
Read
