Journal Article

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

Hu, Li-Qiong, Meng, Qing-Qi, Zhang, Xing-Liang, Li, Si-Ming, Zhang, Hai-Feng, Wang, Min, Feng, Zhen-Cheng

2019

Overview

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.

• Publisher: Hindawi Publishing Corporation,Hindawi,John Wiley & Sons, Inc,Wiley
• Subject: Animals / Anti-Inflammatory Agents - therapeutic use / Caspase / Caspase 1 - metabolism / Caspase-1 / Female / IL-1β / Immunohistochemistry / Immunology / Inflammasomes / Inflammasomes - drug effects / Inflammasomes - metabolism / Inflammation / Inflammation - drug therapy / Inflammation - metabolism / Interleukin 1 / Interleukin 6 / Interleukin-1 - metabolism / Interleukin-6 - metabolism / Ischemia / Nervous system / Neurons / Neurons - cytology / Neurons - drug effects / Neurons - metabolism / Neurosciences / NF-κB protein / NLR Family, Pyrin Domain-Containing 3 Protein - metabolism / Peroxisome proliferator-activated receptors / PPAR gamma - metabolism / Rats / Rats, Sprague-Dawley / Recovery of function / Rodents / Rosiglitazone / Rosiglitazone - therapeutic use / Spinal Cord - cytology / Spinal Cord - metabolism / Spinal cord injuries / Therapeutic applications / Trauma / Traumatic brain injury