Many CNS disorders are associated with astrogliosis. During astrogliosis, astrocytes are thought to increase production of proinflammatory mediators, such as arachidonic acid [63, 64]. Arachidonic acid, which is a substrate for cyclooxygenase-1 (Cox-1) and Cox-2, is released by phospholipase A2 (PLA2). PLA2 and Cox-2 have been associated with neurodegenerative diseases [65, 66]. Interestingly, both secretory PLA2 (sPLA2) and cytosolic PLA2 (cPLA2) contain a PPRE in their promoters. PPARδ expression appears to be abundant in immature cultures of primary rodent astrocytes [30]. In primary rat brain astrocytes, pretreatment of astrocytes with L-165041 attenuated LPS-induced sPLA2 expression, while astrocytes treated simultaneously with L-165041 and LPS displayed increased cPLA2 expression and had no change in sPLA2 expression. As the authors noted, LPS stimulates NF-κB and activator protein-1 (AP-1), which PPARs have been shown to transrepress. It is possible that in this model LPS-induced activation of NF-κB and AP-1 is acting to transrepress PPARδ [35]. Furthermore, LPS-induced Cox-2 expression in rat primary astrocytes may be modulated, in part, by PPARδ. In particular, rosiglitazone, a PPARγ agonist, increased PPARδ expression in cortical astrocytes and led
