The TSPO agonist XBD173 dampens gene transcription of pro-inflammatory markers and reduces microglial neurotoxicity. LPS-activated BV-2 microglial cells were cultured in the presence of various concentrations of XBD173 for 24 h and the pro-inflammatory transcript markers CCL2 (A), IL6 (B), iNOS (C) were determined by real time qRT-PCR. Data show mean ± SD (n = 3/group, measured in triplicates) *P <0.05, **P <0.01, ***P <0.001 XBD173 + LPS versus LPS-treated cells. (D-F), Knock-down of TSPO with two independent shRNAs abrogates the suppressing effects of XBD173 on CCL2 (D), IL6 (E) and iNOS (F) gene expression in BV-2 cells. (G), Production of NO as determined by detection of nitrite from BV-2 microglial cells treated with 50 μM XBD173 in the absence or presence of 50 ng/ml LPS. Data show mean ± SD (n = 9/group) ***P <0.001 XBD173 + LPS versus LPS-treated cells. (H), 661 W photoreceptor cell cultures were treated with conditioned media from BV-2 microglial cells for 48 hours. The supernatant from control-stimulated, 20 μM XBD173-treated, 50 ng/ml LPS-treated, or 20 μM XBD173 + 50 ng/ml LPS-treated cells was added to 661 W photoreceptor cells and apoptosis-related caspase 3/7 activation was determined. Data show mean ± SD (n = 6/group) **P <0.01 XBD173 + LPS versus LPS-treated cells. CCL2, (C-C motif) ligand 2; IL6, interleukin-6; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; NO, nitric oxide.