Astrocytes can regulate how they respond to PPAR ligands through changes in receptor expression. In LPS (lipopolysaccharide)-stimulated astrocytes, PPARγ activation leads to a positive feed-forward signal that increases expression of PPARδ, and PPARδ activation increases expression of PPARα (Aleshin et al., 2009). In turn, PPARα provides a negative-feedback signal inhibiting PPARδ expression (Aleshin et al., 2009). This coordinated signaling helps regulate how PPAR activation influences inflammation (Aleshin et al., 2009). Since the environment surrounding astrocytes can change dramatically with injury or disease, the ability for astrocytes to alter their responses to PPAR ligands allows more precise control of inflammation.
