Differential regulation of peroxisome proliferator activated receptor (ppar) isoforms in murine macrophage J774.2 cell line by cytokines

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dc.contributor.authorGuat Slew, Chew
dc.date.accessioned2015-07-30T05:19:48Z
dc.date.available2015-07-30T05:19:48Z
dc.date.issued2006
dc.description.abstractThe regulation of the PPAR isoforms in macrophage by cytokines is of potentially crucial importance in pathophysiological disorders such as atherosclerosis. In the present study, we evaluated the action of four cytokines on the expression of PPAR mRNA, protein and functional PPAR-DNA binding activity in the murine macrophage J774.2 cell line, a widely used model system for atherosclerosis. Exposure of the cells to TNF-a and IFN-y for 24h, produced a dose-dependent reduction of PPARa and PPARy and a dose-dependent increase of PPAR~/8 mRNA and protein expression. In contrast, IL-1~ produced a dose-dependent increase of PPARa and PPARy and a dose-dependent decrease in PPAR~/8 mRNA and protein expression. However, IL-1a has no effect on all isoforms of PPAR mRNA and protein expression. Electrophoretic mobility shift assay (EMSA) showed a close correlation between the expression of the PPAR mRNA, protein and the functional PPAR-DNA binding activity. Incubation of nuclear extracts with anti-PPAR antibodies in super-shift assay demonstrated the participation of all the three PPAR isoforms'in the binding to PPRE. These results indicate that TNF-a, IFN-y, IL-1~ and IL-1a are important regulators of macrophage PPAR gene and protein expression which affect its DNA binding activities. Thus, this study provides novel insights into the potential mechanisms that may be responsible for the mediator specific regulation of macrophage gene expression through the PPAR isoforms, indicating a possible physiological and potential role for this transcription factor in modulating arterial lipid metabolism and inflammatory response associated with atherosclerosisen_US
dc.identifier.urihttp://hdl.handle.net/123456789/1045
dc.language.isoenen_US
dc.subjectPeroxisome proliferatoren_US
dc.subjectMacrophage J774.2en_US
dc.subjectReceptor (ppar)en_US
dc.titleDifferential regulation of peroxisome proliferator activated receptor (ppar) isoforms in murine macrophage J774.2 cell line by cytokinesen_US
dc.typeThesisen_US
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