Inflammasome: A Pivotal Role in hyperoxia‐induced acute lung injury?

Abstract

The inflammasome is a novel protein complex that stimulates caspase‐1 activation to promote the processing and secretion of pro‐inflammatory cytokines. We hypothesized that hyperoxia induced K+ efflux activates inflammasome through P2X7 receptors (P2X7R) leading to inflammation in hyperoxic acute lung injury (HALI). To test this hypothesis in vitro, we isolated alveolar macrophages from murine lung tissue, exposed cells to hyperoxia (95% oxygen and 5% CO2) and characterized the expression and activation of inflammasome components. We also analyzed the expression of the same molecules in alveolar macrophages obtained from the mice exposed to hyperoxia (100 % oxygen) for 72 hours. Our results showed that hyperoxia induced a significant increase in P2X7 activation and K+ efflux that was associated with inflammasome activation and release of pro‐inflammatory cytokines. P2X7 agonist, ATP enhances hyperoxia induced inflammasome activation and P2X7 antagonist, oxidized ATP inhibits hyperoxia induced inflammasome activation. However, when ATP was scavenged with apyrase, hyperoxia induced inflammasome activation was significantly decreased indicating that the possible involvement of P2X7R. Interestingly inflammasome silence abrogates hyperoxia‐induced secretion of pro‐inflammatory cytokines in‐vitro. Our studies suggest that hyperoxia induces K+ efflux through P2X7 receptor and results in inflammasome activation and secretion of pro‐inflammatory cytokines.