PPAR gamma ligands inhibit TNF-alpha-induced LOX-1 expression in cultured endothelial cells

Endothelial dysfunction or activation, elicited by oxidized low-density lip oprotein (OxLDL), has been implicated in the initiation and progression of atherosclerosis. We elucidated whether tumor necrosis factor-alpha (TNF-alp ha)-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 c onfirmed that both PPAR alpha and PPAR-gamma were expressed in BAEC by reve rse transcription-polymerase chain reaction analysis. Natural PPAR gamma li gand 15-deoxy-Delta (12,14)-prostaglandin J(2) (15d-PGJ(2)) and the thiazol idinediones, pioglitazone and troglitazone, decreased TNF-alpha -induced LO X-1 mRNA expression in BAEC. LOX-1 expression induced by phorbol 12-myristr ate 13-acetate was also inhibited by 15d-PGJ2. In contrast, PPAR alpha liga nds, Wy14643 and fenofibric acid, did not alter TNF-alpha -induced LOX-1 ex pression. TNF-a-induced immunohistochemical staining of LOX-1 was suppresse d by 15d-PGJ2 but not Wy14643. Taken together, PPAR gamma activators inhibi t TNF-a-induced LOX-1 expression in cultured BAEC, which may beneficially i nfluence inflammatory responses in atherosclerosis. (C) 2001 Academic Press .