Aspirin upregulates Suppressor of Cytokine Signaling 3 in glial cells via PPAR α

This study underlines the importance of aspirin in upregulating SOCS3 in astrocytes and microglia. Aspirin increased the expression ofSocs3mRNA and protein in mouse astrocytes and BV ‐2 microglial cells in both a time‐ and dose‐dependent manner. While investigating mechanism, we found thatSocs3 gene promoter harbors PPRE and that aspirin upregulated SOCS3 in astrocytes isolated from PPAR β (‐/‐), but not PPARα (‐/‐), mice. Accordingly, aspirin increased SOCS3in vivo in the cortex of wild type and PPAR β (‐/‐), but not PPARα (‐/‐), mice. Similarly, aspirin treatment increased astroglial and microglial SOCS3 in the cortex of FAD5X, but not FAD5X/PPARα (‐/‐), mice. Finally, recruitment of PPARα by aspirin to the proximal, but not distal, PPRE of theSocs3 promoter suggests that aspirin increases the transcription ofSocs3 gene via PPAR α. This study describes a novel property of aspirin in elevating SOCS3 in glial cells via PPARα and suggests that aspirin may be further considered for therapeutic application in neuroinflammatory and neurodegenerative disorders.This article is protected by copyright. All rights reserved.

Source: Journal of Neurochemistry - July 4, 2019 Category: Neuroscience Authors: Sudipta Chakrabarti, Avik Roy, Tim Prorok, Dhruv Patel, Sridevi Dasarathi, Kalipada Pahan Tags: Original Article Source Type: research