BV2 microglia cells were pre-treated with ADX88178 (5–20μM) or L-AP4 (100μM) for 30 minutes followed by stimulation with or without LPS (20ng/mL) for the next 24 hours. (A-B) LPS stimulation resulted in a significant increase in nitrite production and TNF-α release (####P<0.0001 vs. control for both). ADX88178 treatment significantly reduced LPS-induced nitrite production starting at 5μM (****P<0.0001 vs. LPS), and TNF-α release at 20μM for both 6h and 24h time points (****P<0.0001 vs. LPS). (C-F) mRNA expression of pro-inflammatory mediators in BV2 microglia were measured at 24h. While L-AP4 exerted no anti-inflammatory effect, ADX88178 pre-treatment resulted in a significant downregulation of LPS-induced mRNA levels of miR-155 and TNF-α (***P<0.001 vs. LPS for both), IL-1β (**P<0.01 vs. LPS) and CCL-2 (****P<0.0001 vs. LPS). (G-H) There was no significant changes in mRNA expression levels of anti-inflammatory cytokines IL-10 and Arginase-1. (I) There was no change in protein levels of IL-10 as measured by IL-10 ELISA. (J) There was no cell cytotoxicity at concentrations of ADX88178 used. All values are expressed as mean ± S.E.M. for at least three independent experiments. Data were analyzed using one-way analysis of variance (ANOVA) for multiple comparisons with post hoc Tukey’s test. ##P<0.01, ###P<0.001, ####P<0.0001 in comparison with control; **P<0.01, ***P<0.001, ****P<0.0001 in comparison with LPS.