Shear-Stress Initiates Signal Two of NLRP3 Inflammasome Activation in LPS-Primed Macrophages through Piezo1

was sufficient to induce significant calcium signaling, gasdermin-D cleavage, caspase-1 activity, and IL-1β secretion, all hallmarks of inflammasome activation. Utilizing NLRP3 and caspase-1 knockout iBMDMs, we demonstrated that the NLRP3 inflammasome was primarily activated as a result of shear stress exposure. Quantitative polymerase chain reaction (qPCR), ELISA, and a small molecule inhibitor study aided us in demonstrating that expression of Piezo1, NLRP3, gasdermin-D, IL-1β, and CCL2 secretion were all upregulated in iBMDMs treated with shear stress. This study provides a foundation for further understanding the interconnected pathogenesis of chronic inflammatory diseases and the ability of shear stress to play a role in their progression.