Fig. 4.
a–d VU0360172 attenuates microglial activation in vitro. The anti-inflammatory effects of VU0360172 were assessed using lipopolysaccharide (LPS) or interferon-γ (IFNγ) models of microglial activation in BV2 and primary microglia. a LPS stimulation resulted in a significant increase in TNFα release and nitrite production (*** P < 0.001 vs control for both) in BV2 microglia. VU0360172 treatment significantly reduced LPS-stimulated TNFα release starting at 1 μM (+++ P < 0.001), and LPS-stimulated nitrite production at 20 μM (++ P < 0.01). Similarly, CHPG treatment (positive control) significantly reduced the release of both pro-inflammatory mediators (+++ P < 0.001 vs LPS), whereas VU0360172 treatment alone did not produce TNFα or nitrite. b IFNγ stimulation resulted in a significant increase in TNFα release and nitrite production (*** P < 0.001 vs control for both) in BV2 microglia. VU0360172 treatment significantly reduced IFNγ-stimulated TNFα release starting at 20 μM (+++ P < 0.001), and IFNγ-stimulated nitrite production at 20 μM (++ P < 0.01). Similarly, CHPG treatment (positive control) significantly reduced the release of both pro-inflammatory mediators (+++ P < 0.001 vs IFNγ). Analysis by one-way ANOVA, followed by post-hoc adjustments using a Bonferonni multiple comparisons test. Mean ± S.E.M. (n = 6/treatment). c LPS stimulation resulted in a significant increase in TNFα release and nitrite production (*** P < 0.001 vs control for both) in primary microglia; 20 μM VU0360172 significantly reduced LPS-stimulated TNFα release and nitrite production (+++ P < 0.001), whereas VU0360172 treatment alone had no effect. d IFNγ stimulation resulted in a significant increase in TNFα release and nitrite production (*** P < 0.001 vs control for both) in primary microglia; 20 μM VU0360172 significantly reduced IFNγ-stimulated TNFα release and nitrite production (+++ P < 0.001), whereas VU0360172 treatment alone had no effect. Analysis by 2-way ANOVA, followed by post-hoc adjustments using a Bonferonni multiple comparisons test. Mean ± S.E.M. (n = 6/treatment)