Enhanced Metabolic Inactivation of PGE2 by Selenium in Macrophages is Mediated by the Up regulation of 15‐hydroxy‐prostaglandin dehydrogenase

15‐hydroxy prostaglandin dehydrogenase (15PGDH) is a prostaglandin‐degrading enzyme, which regulates the biological functions of pro‐inflammatory PGE2 leading to the formation of an inactive metabolite, 13,14‐dihydro‐15 keto PGE 2 . Recent and past studies in our laboratory have indicated the ability of micronutrient antioxidant selenium (Se) to regulate the production of PGE 2 , while increase the production of PGD 2 arm of the arachidonic acid pathway, where selenoproteins play a pivotal role. The shunting of PGH 2 to PGD 2 , instead of PGE 2 , upon endotoxin challenge by selenoproteins involves complex regulatory circuits involving the upregulation of H‐PGDS accompanied by the downregulation of mPGES‐1, which catalyzes the production of PGE 2 . Here we demonstrate the ability of Se to upregulate the expression of 15PGDH in a dose‐dependent manner in a murine macrophage model. Treatment of cells with sodium selenite increased the expression of 15PGDH mRNA; while those treated with organo‐Se compounds failed to upregulate 15PGDH suggesting the essential role of selenoproteins. Given that upregulation of 15PGDH is a critical component in the resolution of inflammation, we discuss the implication of upregulation of 15PGDH by Se in a DSS‐induced model of ulcerative colitis. Grant Funding Source : NIH DK077152