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

Abstract EN

Persistent inflammation disrupts functional recovery after spinal cord injury (SCI).

Peroxisome proliferator-activated receptor gamma (PPAR-γ) activation promotes functional recovery in SCI rats by inhibiting inflammatory cascades and increasing neuronal survival.

We sought to clarify the relationship between PPAR-γ activation and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome suppression, and the role of NF-κB in activating the NLRP3 inflammasome in neurons.

In SCI rats, we found that rosiglitazone (PPAR-γ agonist) inhibited the expression of caspase-1.

In in vitro neurons, G3335 (PPAR-γ antagonist) reversed the rosiglitazone-induced inhibition of caspase-1, interleukin 1 (IL-1β), and interleukin 6 (IL-6).

Rosiglitazone inhibited the expression of NLRP3, caspase-1, IL-1β, and IL-6.

However, the activator of NLRP3 could counteract this inhibition induced by PPAR-γ activation.

NF-κB 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-γ, NLRP3, and NF-κB.

These results suggest that PPAR-γ activation exerts an anti-inflammatory effect by suppressing the NLRP3 inflammasome—but not NF-κB—in neurons and that PPAR-γ activation is a promising therapeutic target for SCI.