Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2

In neurodegenerative disease, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been regarded as beneficial. The NSAID, an inhibitor of cyclooxygenase (COX), has been also suggested as a ligand of the peroxisome proliferator-activated receptor (PPAR). In cortical neuron–glial co-cultures, we examined the effect of PPAR agonists on lipopolysaccharide(LPS)-induced neuronal death, which has been known to be NO-dependent. LPS induced iNOS expression and the release of nitric oxide in microglia, and COX-2 expression in neurons. PPAR-γ agonists such as 15d-PGJ 2, ciglitazone and troglitazone prevented LPS-induced neuronal death and abolished LPS-induced NO and PGE 2 release, however PPAR-α agonists such as clofibrate and WY14,643 did not produce the same results. PPAR-γ agonists also reduced LPS-induced iNOS and COX-2 expression, which suggested by interfering with the NF-κB signal pathway.