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

Abstract

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 PGE2. Recent and past studies in our laboratory have indicated the ability of micronutrient antioxidant selenium (Se) to regulate the production of PGE2, while increase the production of PGD2 arm of the arachidonic acid pathway, where selenoproteins play a pivotal role. The shunting of PGH2 to PGD2, instead of PGE2, 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 PGE2. 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