标题：Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：13
页码：7614-7619
DOI：10.1073/pnas.95.13.7614
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is a ligand-dependent transcription factor that has been demonstrated to regulate fat cell development and glucose homeostasis. PPAR{gamma} is also expressed in a subset of macrophages and negatively regulates the expression of several proinflammatory genes in response to natural and synthetic ligands. We here demonstrate that PPAR{gamma} is expressed in macrophage foam cells of human atherosclerotic lesions, in a pattern that is highly correlated with that of oxidation-specific epitopes. Oxidized low density lipoprotein (oxLDL) and macrophage colony-stimulating factor, which are known to be present in atherosclerotic lesions, stimulated PPAR{gamma} expression in primary macrophages and monocytic cell lines. PPAR{gamma} mRNA expression was also induced in primary macrophages and THP-1 monocytic leukemia cells by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Inhibition of protein kinase C blocked the induction of PPAR{gamma} expression by TPA, but not by oxLDL, suggesting that more than one signaling pathway regulates PPAR{gamma} expression in macrophages. TPA induced the expression of PPAR{gamma} in RAW 264.7 macrophages by increasing transcription from the PPAR{gamma}1 and PPAR{gamma}3 promoters. In concert, these observations provide insights into the regulation of PPAR{gamma} expression in activated macrophages and raise the possibility that PPAR{gamma} ligands may influence the progression of atherosclerosis.
