Differential inflammasome-mediated response against amyloid-beta (Ab) exposure from cholesterol-primed neuronal and microglial cells
| Autor: | Dios, Cristina de, Roca-Agujetas, Vicente, Abadin, Xenia, Jiménez Martínez, Marina, Colell Riera, Anna |
|---|---|
| Rok vydání: | 2021 |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Resumen del trabajo presentado en el 43rd Annual Meeting of the SEBBM, celebrado en Barcelona (España) del 19 al 22 de julio de 2021 Neuroinflammation is emerging as a real cause of Alzheimer¿s disease (AD) progression. Mainly mediated by microglia, the inflammatory response acts to remove Ab deposits and dead cells; however, improper activation of these cells may lead to a worsening of the pathology. The factors that influence the activation status of glia cells are still unraveled. Mitochondrial oxidative stress has been remarked as an activator of inflammasomes, pathogen/damage-induced assemblies that drive the inflammatory response and gasdermin-mediated cell death (pyroptosis). In this line, previous studies from our group have shown that cholesterol-induced depletion of mitochondrial GSH levels and subsequent enhanced mitochondrial oxidative stress elicited by Aß leads to a worsening of pathology in APPPSEN1 mice. Bearing this into consideration, we aimed to study the role of cholesterol on Aß-induced inflammasome activation. For this purpose, the neuroblastoma cell line SH-SY5Y and microglia cell line SIM-A9 were cholesterol- enriched before exposure to LPS+muramyl dipeptide, Aß, or serum deprivation. In SH-SY5Y cells, the rise of intracellular cholesterol stimulated the oligomerization of the inflammasome components and a shift to pyroptosis. The cholesterol-enhanced cell death was prevented by both caspase-1 inhibitor and GSH ethyl ester treatment. In contrast, cholesterol-enriched microglia showed a neuroprotective behavior accompanied by enhanced phagocytosis after exposure to inflammasome inducers. Remarkably, the microglial phagocytic function was completely abolished when cells were incubated with conditioned media from cholesterol plus Aß-treated SH-SY5Y cells. Overall, these results highlight the differential contribution of cholesterol to Aß-induced inflammasome activation in neuronal and microglial cells, which may ultimately condition the inflammatory response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|