Endothelial nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis (851.5)

The present study aimed at exploring the mechanisms by which NOD-like receptor protein 3 (Nlrp3) inflammasomes are activated to result in endothelial dysfunction and coronary arteritis induced by Lactobacillus casei (L. casei) cell wall fragments (LCWE). Endothelial dysfunction and vascular lesion were observed during coronary arteritis in mice treated with LCWE, as shown by media thickening, increases in vascular cell adhesion protein 1 (VCAM-1) expression, and enhanced adhesion of inflammatory cells to the endothelium including macrophages, neutrophils and T cells. Accompanied with these changes, the inflammasome activation was also shown in the coronary arterial endothelium of these mice, which was characterized by a marked increase in caspase-1 activity and interleukin-1β (IL-1β) production. In isolated cultured endothelial cells (ECs), LCWE induced Nlrp3 inflammasome formation, caspase-1 activation and IL-1β production, which were blocked by Nlrp3 gene silencing or lysosome membrane stabilizing agent...