Selenoprotein activity alters eicosanoid biosynthesis in macrophages (P5042)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.180-180.4
• Main Authors: Mattmiller, Sarah, Sordillo, Lorraine, Carlson, Bradley
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.180.4

Selenium (Se) exerts anti-inflammatory properties largely through the activity of antioxidant selenoproteins. However, the effect of reduced selenoprotein activity on the eicosanoid signaling network is unknown. Therefore, the objective of this study was to characterize the biosynthesis of eicosanoids that enhance or resolve inflammation as a function of selenoprotein activity. Macrophages cultured in Se-sufficient or Se-deficient media or macrophages obtained from selenoprotein conditional knockout mice were used to assess inflammatory markers and eicosanoids. Reduced selenoprotein activity significantly increased free radical accumulation, pro-inflammatory cytokines, and cyclooxygenase and lipoxygenase enzyme expression. Reduced selenoprotein activity significantly diminished the production of anti-inflammatory eicosanoids, lipoxin A4 and protectin, hydroxyl eicosanoids from arachidonic acid, and hydroxyl and ketone eicosanoids from linoleic acid (LA). Since LA is a predominant lipid in the western diet and LA-derived metabolites were produced in substantial amounts by macrophages, studies are currently underway to determine the inflammatory effect of the LA ketone, 9oxoODE. Future studies aim at determining if LA eicosanoids are oxidized by lipoxygenases or by non-enzymatic means when selenoprotein activity is reduced. A better understanding of how Se regulates eicosanoid biosynthesis may uncover nutritional intervention strategies to counteract uncontrolled inflammation.