PPAR-γ Activation Exerts an Anti-inflammatory Effect by Suppressing the NLRP3 Inflammasome in Spinal Cord-Derived Neurons

Persistent inflammation disrupts functional recovery after spinal cord injury (SCI). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) activation promotes functional recovery in SCI rats by inhibiting inflammatory cascades and increasing neuronal survival. We sought to clarify the relationship between PPAR-gamma activation and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome suppression, and the role of NF-kappa B in activating the NLRP3 inflammasome in neurons. In SCI rats, we found that rosiglitazone (PPAR-gamma agonist) inhibited the expression of caspase-1. In in vitro neurons, G3335 (PPAR-gamma antagonist) reversed the rosiglitazone-induced inhibition of caspase-1, interleukin 1 (IL-1 beta), and interleukin 6 (IL-6). Rosiglitazone inhibited the expression of NLRP3, caspase-1, IL-1 beta, and IL-6. However, the activator of NLRP3 could counteract this inhibition induced by PPAR-gamma activation. NF-kappa B did not participate in the process of rosiglitazone-induced inhibition of NLRP3. Consistent with our in vitro results, we verified that locomotor recovery of SCI rats in vivo was regulated via PPAR-gamma, NLRP3, and NF-kappa B. These results suggest that PPAR-gamma activation exerts an anti-inflammatory effect by suppressing the NLRP3 inflammasomebut not NF-kappa B in neurons and that PPAR-gamma activation is a promising therapeutic target for SCI.