REGULATION OF THE INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THP-1 CELLS BY LIGANDS OF THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR γ

Cytokine ◽  
2002 ◽  
Vol 18 (6) ◽  
pp. 320-328 ◽  
Author(s):  
Christoph A Meier ◽  
Rachel Chicheportiche ◽  
Cristiana E Juge-Aubry ◽  
Magali G Dreyer ◽  
Jean-Michel Dayer
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interleukin 1 Receptor Antagonist

scholarly journals Upregulation of IL-1 Receptor Antagonist by Aspirin in Glial Cells via Peroxisome Proliferator-Activated Receptor-Alpha

2021 ◽  
pp. 1-15
Author(s):  
Sudipta Chakrabarti ◽  
Tim Prorok ◽  
Avik Roy ◽  
Dhruv Patel ◽  
Sridevi Dasarathi ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Glial Cells ◽  
Interleukin 1 ◽  
Gene Promoter ◽  
Brain Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Primary Mouse ◽  
The Brain

Background: Neuroinflammation is a recognized aspect of Alzheimer’s disease (AD) and other neurological illnesses. Interleukin 1 receptor antagonist (IL-1Ra) is an anti-inflammatory molecule, which inhibits inflammatory molecules in different cells including brain cells. However, mechanisms for upregulating IL-1Ra in brain cells are poorly understood. Objective: Since aspirin is a widely available pain reliever that shows promise beyond its known pain-relieving capacity, we examined whether aspirin could upregulate the IL-1Ra in the brain. Methods: We employed PCR, real-time PCR, western blot, immunostaining, chromatin immunoprecipitation (ChIP), and lentiviral transduction in glial cells. 5xFAD mice, an animal model of AD, were treated with aspirin orally via gavage. Results: Aspirin increased the expression of IL-1Ra mRNA and protein in primary mouse astrocytes and mouse BV-2 microglial cells. While investigating the mechanism, we found that the IL-1Ra gene promoter harbors peroxisome proliferator response element (PPRE) and that aspirin upregulated IL-1Ra in astrocytes isolated from peroxisome proliferator-activated receptor-beta knockout (PPARβ –/–), but not PPARα –/–, mice. Moreover, we observed that aspirin bound to tyrosine 314 residue of PPARα to stimulate IL-1Ra and that aspirin treatment also increased the recruitment of PPARα to the IL-1Ra promoter. Accordingly, aspirin increased IL-1Ra in vivo in the brain of wild type and PPARβ –/–, but not in PPARα –/– mice. Similarly, aspirin treatment also increased astroglial and microglial IL-1Ra in the cortex of 5xFAD, but not 5xFAD/PPARα –/– mice. Conclusion: Aspirin may reduce the severity of different neurological conditions by upregulating IL-1Ra and reducing the inflammation.

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