MicroRNA-451 Attenuates the Inflammatory Response of Activated Microglia by Downregulating Nucleotide Binding Oligomerization Domain-Like Receptor Protein 3

Abstract

Spinal cord injury is the most common problem encountered during spinal surgery. After the initial trauma, the disruption of the blood-brain barrier and subsequent microglia activation result in extensive inflammatory responses. Inflammasomes are large protein complexes that are essential during inflammation. One of the most studied inflammasome components, nucleotide binding oligomerization domain-like receptor protein 3 (NLRP; nucleotide binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3), is widely expressed in the central nervous system. Previous research has shown that microRNA-451 (miR-451) might play a role in regulating inflammatory conditions. Using bioinformatics analysis, we found that NLRP3 is a direct target of miR-451. This in silico prediction was confirmed using dual-luciferase reporter gene assays. To further demonstrate that miR-451 influenced microglial NLRP3 production, we activated microglial cells with lipopolysaccharides. Activating microglial cells with lipopolysaccharides resulted in the production of NLRP3 inflammasomes and the secretion of the proinflammatory cytokines interleukin-1β and interleukin-18. We were able to demonstrate that overexpression of miR-451 suppressed this NLRP3-induced proinflammatory cascade of events. Our findings have highlighted the potential anti-inflammatory role of miR-451 in reducing the secondary neuronal damage after spinal cord injury.