MiRNA-338-3p inhibit neuroinflammation in the corpus callosum of ICV-LPS rats via STAT1 signal pathway

Abstract

Abstract Neuroinflammation is common characteristics of many neurological disorders, which is associated with the activation of astrocytes and microglia. This study aimed to investigate the potential mechanism that miR-338-3p negatively modulate neuroinflammation in the corpus callosum (CC) of rats after Lipopolysaccharide (LPS) injection. We here reported that the decreased levels of miR-338-3p were detected using qRT-PCR and the upregulated expression of TNF-α and IL-1β was measured by ELISA in the cerebrospinal fluid (CSF) in patients with intracranial infection (ICI). A negative association between miR-338-3p and TNF-α or IL-1β was revealed by Pearson correlation analysis. Sprague-Dawley (SD) rats were injected with LPS (50ng) into intracerebroventricular (ICV), following which increased expression of TNF-α and IL-1β and reduction of miR-338-3p expression were observed in the CC. Overexpression of miR-338-3p through injection of AAV-miR-338-3p plasmid into ICV might saliently inhibit the expression of TNF-α and IL-1β in the astrocytes and microglia in the CC of ICV-LPS rats. In vitro cultured astrocytes and BV2 cells transfected with mimic-miR-338-3p produced fewer TNF-α and IL-1β after LPS administration. Direct interaction between miR-338-3p and STAT1 mRNA was validated by biological information analysis and dual luciferase assay. Furthermore, STAT1 pathway was found to be implicated in inhibition of neuroinflammation induced by mimic miR-338-3p in the astrocytes and BV2 cells. Taken together, our results suggest that miR-338-3p suppress the generation of inflammatory mediators in astrocyte and BV2 cells induced by LPS exposure through STAT1 signal pathway. MiR-338-3p would act as a potential therapeutic strategy to mitigate the occurrence of neuroinflammation.