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

Abstract

Background: Some nanoparticles are known to induce endoplasmic reticulum (ER) stress and lead to cell death. Results: Silver nanoparticles induce ATF-6 degradation, leading to activation of the NLRP-3 inflammasome and pyroptosis. Conclusion: ATF-6 is an important target to silver nanoparticles. Significance: Our results provide a new link between ER stress and activation of the NLRP-3 inflammasome.

Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1 Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State

“…Intracellular crystals, such as those formed by cholesterol or uric acid, have been implicated in the activation of the NLRP3-Casp 1 inflammasome, which plays a major role in the pathogenesis of chronic inflammatory disorders (14,33,34). The uptake of other nano-and microparticles has also been reported to cause inflammasome activation in macrophages (35)(36)(37). Therefore, to assess whether the bioaccumulation of CFZ crystals leads to activation of the inflammasome, we measured and compared cleaved Casp 1 and IL-1␤ in organs that bioaccumulate CFZ-i.e., the liver, spleen, and lungs-and kidneys, that do not accumulate CFZ, after 2 and 8 weeks of either CFZ or control treatment.…”

“…Of noteworthy significance, the formation and accumulation of cholesterol monohydrate and monosodium urate crystals have been implicated in the pathogenesis of chronic inflammatory diseases, such as atherosclerosis, nonalcoholic steatohepatitis (NASH) (34), and gout (43). Moreover, other artificial nano-and microparticles, such as silica crystals (37), aluminum salt crystals (44), silver nanoparticles (35), poly(lactide-co-glycolide) (PLG), and polystyrene microparticles (36), have also been reported to cause inflammasome activation in macrophages. At the cellular level, the aforementioned particles or crystals are known to augment Toll-like receptor signaling and activate the NLRP3 inflammasome via lysosomal destabilization, which leads to Casp 1 activation and the production of cleaved IL-1␤ (13,14).…”

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

“…In addition to the analyses of the induction of proinflammatory factors we also examined whether cell stress might occur in ECs after exposure to nanoparticles. Several studies have previously shown induced endoplasmic reticulum (ER) stress in different cell types after treatment with silverdoped silica NPs, 40 silver NPs 41,42 or polystyrene nanospheres. 43 Chen et al showed that zinc oxide NPs triggered ER stress in HUVEC 44 and gold NPs were shown to induce stress signaling in K562 cells.…”

Construction of a tissue engineered intervertebral disc with high biological activity using an allogeneic intervertebral disc supplemented with transfected nucleus pulposus cells expressing exogenous dopamine beta-hydroxylase

“…The volume of the cell suspension injected was 20 μL. Then, 5 x 10 5 , 5 x 10 6 , and 5 x 10 7 cells/mL suspensions were prepared with the transfected NP cells obtained according to a previously reported method (Simard et al, 2015). A 5 x 10 4 cells/mL cell suspension was prepared for the control group.…”