{Reference Type}: Journal Article
{Title}: The ROS/TXNIP/NLRP3 pathway mediates LPS-induced microglial inflammatory response.
{Author}: Zhao Q;Liu G;Ding Q;Zheng F;Shi X;Lin Z;Liang Y;
{Journal}: Cytokine
{Volume}: 181
{Issue}: 0
{Year}: 2024 Sep 18
{Factor}: 3.926
{DOI}: 10.1016/j.cyto.2024.156677
{Abstract}: <B>BACKGROUND: </B>Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction activated by microglia. The potential pathological changes of SAE are complex, and the cellular pathophysiological characteristics remains unclear. This study aims to explore the ROS/TXNIP/NLRP3 pathway mediated lipopolysaccharide (LPS)-induced inflammatory response in microglia.<BR><B>METHODS: </B>BV-2 cells were pre-incubated with 10 μM N-acetyl-L-cysteine (NAC) for 2 h, which were then reacted with 1 μg/mL LPS for 24 h. Western blot assay examined the protein levels of IBA1, CD68, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. The contents of inflammatory factor were detected by ELISA assay. The co-immunoprecipitation assay examined the interaction between TXNIP and NLRP3.<BR><B>RESULTS: </B>LPS was confirmed to promote the positive expressions of IBA1 and CD68 in BV-2 cells. The further experiments indicated that LPS enhanced ROS production and NLRP3 inflammasome activation in BV-2 cells. Moreover, we also found that NAC partially reversed the facilitation of LPS on the levels of ROS, IL-1β, IL-18, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. NAC treatment also notably alleviated the interaction between TXNIP and NLRP3 in BV-2 cells.<BR><B>CONCLUSIONS: </B>ROS inhibition mediated NLRP3 signaling inactivation by decreasing TXNIP expression.