PPARgamma but not PPARalpha ligands are potent repressors of major histocompatibility complex class II induction in atheroma-associated cells.

Details

Serval ID
serval:BIB_6EAD17000C86
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PPARgamma but not PPARalpha ligands are potent repressors of major histocompatibility complex class II induction in atheroma-associated cells.
Journal
Circulation Research
Author(s)
Kwak B.R., Myit S., Mulhaupt F., Veillard N., Rufer N., Roosnek E., Mach F.
ISSN
1524-4571[electronic]
Publication state
Published
Issued date
2002
Volume
90
Number
3
Pages
356-362
Language
english
Abstract
Peroxisome proliferator-activated receptors (PPARs) are essential in glucose and lipid metabolism and are implicated in metabolic disorders predisposing to atherosclerosis, such as diabetes and dyslipidemia. Conversely, antidiabetic glitazones and hypolipidemic fibrate drugs, known as PPARgamma and PPARalpha ligands, respectively, reduce the process of atherosclerotic lesion formation, which involves chronic immunoinflammatory processes. Major histocompatibility complex class II (MHC-II) molecules, expressed on the surface of specialized cells, are directly involved in the activation of T lymphocytes and in the control of the immune response. Interestingly, expression of MHC-II has recently been observed in atherosclerotic plaques, and it can be induced by the proinflammatory cytokine interferon-gamma (IFN-gamma) in vascular cells. To explore a possible role for PPAR ligands in the regulation of the immune response, we investigated whether PPAR activation affects MHC-II expression in atheroma-associated cells. In the present study, we demonstrate that PPARgamma but not PPARalpha ligands act as inhibitors of IFN-gamma-induced MHC-II expression and thus as repressors of MHC-II-mediated T-cell activation. All different types of PPARgamma ligands tested inhibit MHC-II. This effect of PPARgamma ligands is due to a specific inhibition of promoter IV of CIITA and does not concern constitutive expression of MHC-II. Thus, the beneficial effects of antidiabetic PPARgamma activators on atherosclerotic plaque development may be partly explained by their repression of MHC-II expression and subsequent inhibition of T-lymphocyte activation.
Keywords
Arteriosclerosis/immunology, Arteriosclerosis/metabolism, Cells, Cultured, Dose-Response Relationship, Drug, Endothelium, Vascular/cytology, Endothelium, Vascular/metabolism, Flow Cytometry, Gene Expression Regulation/drug effects, Gene Expression Regulation/physiology, Genes, Reporter, Histocompatibility Antigens Class II/genetics, Histocompatibility Antigens Class II/metabolism, Humans, Hypoglycemic Agents/pharmacology, Interferon-gamma/pharmacology, Ligands, Lymphocyte Activation/drug effects, Lymphocyte Activation/immunology, Lymphocyte Culture Test, Mixed, Monocytes/cytology, Monocytes/drug effects, Prostaglandin D2/analogs & derivatives, Prostaglandin D2/pharmacology, RNA, Messenger/metabolism, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/metabolism, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, Transcription Factors/genetics, Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2009 8:14
Last modification date
20/08/2019 14:27
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