Involvement of purinergic 2X₄ receptor in glycoprotein 120‐induced pyroptosis in dorsal root ganglia

Abstract

Pyroptosis is a type of programmed cell death, displaying caspase-1-dependent and pro-inflammatory features. Purinergic 2X₄ (P2X₄ ) receptor activation in response to high-adenosine triphosphate release can induce inflammation. Envelope glycoprotein 120 (gp120) of human immunodeficiency virus type 1 is considered one of the primary pathogens leading to neuronal injury. In this study, we investigated the possible role of P2X₄ receptor activation in gp120-triggered pyroptosis in cultured satellite glial cells (SGCs) of rat dorsal root ganglia (DRG). MTS assay, TdT-mediated dUTP Nick-end labeling assay, real-time RT-PCR, and western blotting et al. methods were used. The results indicated that the expression of P2X₄ receptor in SGCs of DRG was up-regulated upon cultured with gp120 for 24 h. The highest decrease in viability of SGCs due to gp120 treatment was accompanied by marked increases of positive pyroptosis cells and cellular lactate dehydrogenase release, elevated levels of interleukin-1β, interleukin-18, active caspase-1 and NOD-like receptor family, pyrin domain containing 1, and enhanced phosphorylation of p38MAPK. These abnormal changes because of gp120 were significantly inhibited and cell viability was markedly improved when SGCs of DRG were treated with short hairpin RNAs targeting P2X₄ receptor. Our data suggest that silencing of P2X₄ receptor may act effectively against gp120-induced pyroptosis mediated by the activation of NOD-like receptor family, pyrin domain containing 1 inflammasome and caspase-1 signaling in SGCs of DRG.