Bioactive Flavonoid Extract Suppresses NLRP3 Activation and Inflammation in 2D and 3D Lung Models

Abstract

Inflammasome activation plays a critical role in lung inflammation, with the NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3) inflammasome serving as a key mediator of inflammatory cytokine release and pyroptotic cell death. This study investigates the effects of a bioactive flavonoid extract (BFE), as a potential modulator of NLRP3-mediated inflammation using THP-1 derived macrophages, A549 lung cells (2D cells), and lung organoids (3D cells). Cells were primed with lipopolysaccharide (LPS), treated with BFE, and then activated with nigericin to induce NLRP3 activation and examine BFEs effects. Markers of inflammation, including presence of ASC specks (3D models), reactive oxygen species production (ROS) (2D models), caspase-1 activity (2D and 3D models), and IL-1{beta} release (2D and 3D models) were measured to assess the extent of inflammasome activation in several treatment conditions. By integrating 2D and 3D lung models, this work provides insight into the NLRP3 inflammasome axis in lung inflammation and explores BFE as a potential therapeutic strategy for inflammasome-driven pulmonary inflammatory processes.