Differential Regulation of Peroxisome Proliferator Activated Receptor Isoforms in the Macrophage J774.2 Cell Line By Cytokines
DOI:
https://doi.org/10.7439/ijbr.v6i12.2669Abstract
The regulation of the peroxisome proliferator-activated receptor (PPAR) isoforms in macrophages by cytokines is of potentially crucial importance in the pathogenesis of atherosclerosis. However, the precise mechanisms by which different cytokines modulate the expression of macrophage PPAR isoforms activity are still poorly understood. In the present study, we evaluated the action of four cytokines on the expression of PPAR isoforms 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 tumour necrosis factor alpha (TNF?) and interferon gamma (IFN?) for 24h, produced a dose-dependent reduction of PPAR alpha and gamma isoforms (PPAR? and PPAR?) and a dose-dependent increase of the PPAR beta/delta isoforms (PPAR?/?) mRNA and protein expression. In contrast, interleukin-1 beta (IL-1?) produced a dose-dependent increase of PPAR? and PPAR? and a dose-dependent decrease in PPAR?/? mRNA and protein expression. However, IL-1? 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 the peroxisome proliferator response elements (PPRE). These results indicate that TNF?, IFN?, IL-1? and IL-1? 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 atherosclerosis.Downloads
Download data is not yet available.
Downloads
Published
2015-12-30
Issue
Section
Original Research Articles
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
- An author must submit Copyright form After acceptance of the article.
How to Cite
1.
Differential Regulation of Peroxisome Proliferator Activated Receptor Isoforms in the Macrophage J774.2 Cell Line By Cytokines. Int Jour of Biomed Res [Internet]. 2015 Dec. 30 [cited 2024 Oct. 18];6(12):972-81. Available from: https://ssjournals.co.in/index.php/ijbr/article/view/2669