Fig. 4: Activation of NLRP3 inflammasome induced by liver-derived ApoE4.

A Experimental design: 1 h before the hepatic portal vein injection mice in old group were randomly intraperitoneally injected with normal saline (NS), 20 μg/kg/day L-thy, 200 mg/kg/day ApoE4 inhibitor PH-002, lasting for 2 weeks. Two months old mice randomly underwent thyroidectomy or sham surgery. Four weeks after surgery mice were injected with lenti-Arg1-ApoE4-eGFP vector through hepatic portal veins for 2 weeks. B Representative Western blots of NLRP3, caspase-1, GSDMD, pro-caspase-1 and ASC collected from the proteins in cortex and hippocampus. C–G Expression ratios of NLRP3 C, caspase-1 D, GSDMD E, pro-caspase-1, F and ASC G normalised to β-actin are plotted as mean ± SD, n = 6. H Immunofluorescence images of GSDMD (green) co-stained with GFAP (red) and DAPI (blue) in cortex (above two rows) and hippocampus (lower two rows). Scale bar = 50 μm. I Immunofluorescence intensity of GSDMD normalised to adult group shown as mean ± SD, n = 6. One-way ANOVA for comparisons including more than two groups; unpaired two-tailed t-test for two-group comparisons. As comparison with adult group, *p < 0.05, **p < 0.01, ***p < 0.001.