Silver Nanoparticles Induce Degradation of the Endoplasmic Reticulum Stress Sensor Activating Transcription Factor-6 Leading to Activation of the NLRP-3 Inflammasome

摘要: In the past decade, increasing amount of nanoparticles (NP) and nanomaterials used in multiple applications led scientific community to investigate potential toxicity NP. Many studies highlighted cytotoxic effects various NP, including titanium dioxide, zinc oxide, silver (AgNP). a few studies, endoplasmic reticulum (ER) stress was found be associated with NP cytotoxicity leading apoptosis different cell types. this study, we report for first time that 15 nm (AgNP15), depending on concentration, induced signature ER markers human THP-1 monocytes rapid response degradation ATF-6 sensor. Also, AgNP15 pyroptosis activation NLRP-3 inflammasome as demonstrated by processing increased activity caspase-1 secretion IL-1β ASC (apoptosis-associated speck-like protein containing CARD domain) pyroptosome formation. Transfection cells siRNA targeting decreased AgNP15-induced production. The absence caspase-4 expression resulted significant reduction pro-IL-1β. However, significantly higher caspase-4-deficient when compared WT cells. Inhibition Site-2 protease inhibitors completely blocked effect IL-1β, indicating is crucial induction type death. We conclude induce sensor ATF-6, regulated monocytes.