PPARgamma ligands inhibit TNF-alpha-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, lectin-like 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 PPARalpha and PPARgamma were expressed in BAEC by reverse transcription-polymerase chain reaction analysis. Natural PPARgamma 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-PGJ(2). In contrast, PPARalpha ligands, Wy14643 and fenofibric acid, did not alter TNF-alpha-induced LOX-1 expression. TNF-alpha-induced immunohistochemical staining of LOX-1 was suppressed by 15d-PGJ(2) but not Wy14643. Taken together, PPARgamma activators inhibit TNF-alpha-induced LOX-1 expression in cultured BAEC, which may beneficially influence inflammatory responses in atherosclerosis.
Chiba
Y
Y
Department of Internal Medicine, University of Tokyo School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Ogita
T
T
Ando
K
K
Fujita
T
T
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004336:Drug Antagonism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051131:Receptors, Oxidized LDL; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002839:Chromans; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000077288:Troglitazone; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2; D000077205:Pioglitazone