Fig. 4

Pharmacological agents and caspase inhibitors partially reversed loratadine-induced cell death. A Pyroptotic cell changes, such as cell swelling and membrane blebbing, were noted with red arrows in A549 cells treated with H-loratadine as well as different cell death inhibitors. B Validation of PPARG as a promoter of GSDMD expression using a luciferase reporter assay. The promoter region of GSDMD was cloned upstream of the luciferase gene in the pGL3-Basic vector. The PPARG expression vector (vec PPARγ) was used to upregulate PPARγ expression. Bar graph representing relative luciferase activity in cells. Luciferase activity was normalized to Renilla luciferase activity for each sample. Data are presented as the mean ± SD of three independent experiments. ***P < 0.001 compared to control. C-D A549 and NCI-H1299 cells were treated with different doses of loratadine combined with cell death inhibitors or caspase inhibitors. The indicated proteins were analyzed by Western blotting. GSDME-FL, full-length GSDME; GSDME-N, GSDME N-terminal domain; C1 IN, caspase 1 inhibitor (ac-YVAD-cmk); C3 IN, caspase 3 inhibitor (z-DEVD-fmk); C8 IN, caspase 8 inhibitor (z-IETD-fmk); Z-VAD pan caspase inhibitor (z-VAD-fmk); M-LOR, moderate dose of loratadine; H-LOR, high dose of loratadine