Cyclooxygenase-2 Is Induced in Monocytes by Peroxisome Proliferator Activated Receptor γ and Oxidized Alkyl Phospholipids from Oxidized Low Density Lipoprotein
作者： Aaron V. Pontsler , Andy St. Hilaire , Gopal K. Marathe , Guy A. Zimmerman , Thomas M. McIntyre
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摘要: Low density lipoprotein (LDL) oxidation and monocyte infiltration of the vessel wall underlie atherogenesis. These cells express cyclooxygenase-2, but way oxidized LDL stimulates cyclooxygenase-2 transcription is unknown. Oxidized LDL, oxidatively fragmented phospholipids isolated from a synthetic alkylphospholipid (azPC) that potent peroxisome proliferator activated receptor (PPAR) γ agonist, or PPARγ agonist rosiglitazone all induced expression enhanced prostaglandin E2 (PGE2) secretion in primary human monocytes. The inhibitor NS398 blocked PPARγ-induced PGE2 secretion. Phospholipase A1 A2 digestion shows alkylphospholipids, not fatty acids, were relevant agonists. upstream PPAR-responsive element (PPRE) was required for induction luciferase reporter by phospholipids, azPC, rosiglitazone, (COX-2 PPRE)3-luciferase responsive to these Circulating monocytes do contain PPARγ, rapidly (
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