PPARγ ligands inhibit TNF-α-induced LOX-1 expression in cultured endothelial cells

Endothelial dysfunction or activation, elicited by oxidized low-density lipoprotein (OxLDL), has been implicated in the initiation and progression of atherosclerosis. We elucidated whether tumor necrosis factor-alpha (TNF-alpha)-induced endothelial OxLDL receptor, lectinlike OxLDL receptor-1 (LOX-1), mRNA expression is modified by peroxisome proliferator-activated receptor (PPAR) activators in cultured bovine aortic endothelial cells (BAEC). We confirmed that both PPAR alpha and PPAR-gamma were expressed in BAEC by reverse transcription-polymerase chain reaction analysis. Natural PPAR gamma ligand 15-deoxy-Delta (12,14)-prostaglandin J(2) (15d-PGJ(2)) and the thiazolidinediones, pioglitazone and troglitazone, decreased TNF-alpha -induced LOX-1 mRNA expression in BAEC. LOX-1 expression induced by phorbol 12-myristrate 13-acetate was also inhibited by 15d-PGJ2. In contrast, PPAR alpha ligands, Wy14643 and fenofibric acid, did not alter TNF-alpha -induced LOX-1 expression. TNF-a-induced immunohistochemical staining of LOX-1 was suppressed by 15d-PGJ2 but not Wy14643. Taken together, PPAR gamma activators inhibit TNF-a-induced LOX-1 expression in cultured BAEC, which may beneficially influence inflammatory responses in atherosclerosis. (C) 2001 Academic Press.