Blocking Caspase-1/Gsdmd and Caspase-3/-8/Gsdme pyroptotic pathways rescues silicosis in mice
Fig 6
In vivo administration of caspase inhibitors upon silica stimulation reduces immune cell infiltration and silicosis pathology.
a, Caspase inhibitors intervene strategy. b, Western blot of Gsdmd, Gsdme, Caspase-1, Caspase-3, Caspase-6, Caspase-8, IL-1β and IL-18 activation in collected BALF from mice treated as indicated, n = 2. c, Relative number of macrophages, monocytes and neutrophils in the whole lungs of mice 14 days after instillation of PBS, silica and the indicated inhibitors, n = 5. d, The number of macrophages, monocytes and neutrophils in lung tissue of mice that installed with PBS, silica and indicated inhibitors, n = 5. e, Immunofluorescence images of macrophages (CD11b+F480+), neutrophils (CD11b+Ly6G+) and monocytes (CD11b+Ly6C+) in lung tissues of mice. Arrowheads indicate the infiltrated immune cells that labelled with antibodies against CD11b (green), F4/80 (red) and Ly6G/6C (red). DAPI (grey) localizes with the nuclei. The scale bar represents 50 μm. f, H&E (left) and Masson (right) staining of the indicated mouse lung sections 14 days after the initial silica challenge. The scale bar represents 100 μm. z-VAD, z-VAD-FMK; 3is, VX765+z-DEVD-FMK+z-IETD-FMK. z-VAD-FMK, pan-caspase inhibitor; VX765, Caspase-1 inhibitor; z-DEVD-FMK, Caspase-3 inhibitor; z-IETD-FMK, Caspase-8 inhibitor. The total dosage of injected caspase inhibitor(s) was 0.25 mg per mouse administered once. Results are expressed as mean ± SD from three independent experiments. NS, not significant; *P<0.05, **P<0.01 and ***P<0.001.