Fig. 3

A siRNA screen in human microglia revealed that caspase-3/7 knockdown inhibits LDH release associated with pyroptosis. a–h Microglia were transfected with either universal non-coding siRNA (NC siRNA) or a cocktail of three different siRNAs targeting GSDMD (a), caspase-1 (b), caspase-4 (c), caspase-8 (d), caspase-9 (e), GSDME (f), caspase-3 (g), or caspase-7 (h) prior to nigericin exposure (5 μM, 4 h) and cell supernatants were measured for LDH activity. To account for overlapping substrate profiles of caspase-3 and -7, supernatant LDH activity was measured in microglia transfected with either universal non-coding siRNA (NC siRNA) or a cocktail of six different siRNAs targeting caspase-3 and -7 prior to nigericin (5 μM, 4 h) (i) or ATP (100.0 μM, 24 h) (j) exposure. Data shown represent mean MFI ± SEM for a representative human donor (*p < 0.05, **p < 0.01, ****p < 0.0001)