Fig. 4

ADAM10 inhibitor attenuates IL-1β-, TNF-α- and IFN-γ-induced sCX3CL1 release. Human astrocytes (a–f grown in speciality media, g–i grown in speciality media) were serum starved for 3 h and pre-treated with a combination of the ADAM10/17 inhibitor (BMS-561392; 1 μM), specific TACE inhibitor (BMS-566394; 1 μM) or specific ADAM10 inhibitor (GI 254023X; 1 μM) for 30 min. Cells were then stimulated with either IL-1β (100 pg/ml) (a, d, g), TNF-α (10 ng/ml) (b, e, h) or IFN-γ (10 ng/ml) (c, f, i) for 18 h. Quantification of CX3CL1 ELISA revealed a significant decrease in sCX3CL1 when pre-treated with the ADAM10/17 inhibitor and specific ADAM10 inhibitor. No significant difference was seen with the specific ADAM17 inhibitor. ###p < 0.001 compared to own control; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to the matched treated group. Values expressed as averages ± SEM; n = 4–8, each condition done in duplicate (one-way ANOVA and Tukey’s post hoc test)