Peg 400

Dasatinib (Selleck) was dissolved in DMSO at 60 mg/ml and stored in aliquots at −20 °C. On each treatment day, aliquots were thawed and diluted in PBS with 5% polyethylene glycol (PEG-400; Sangon Biotech) and 1% Tween-λ80(Sangon Biotech) immediately before use. Control mice were treated with an equivalent concentration of DMSO dissolved in PBS. Then the diluted Dasatinib (15 mg/kg) or DMSO was injected into the peritoneal cavity of mice every day during the DSS feeding.

The m-PEA was obtained from Wuxi Cima Science (Wuxi, China). Hematoxylin-Eosin (HE) staining kit was purchased from Solarbio Life Sciences (Beijing, China). Oil Red O was from Sigma-Aldrich (Shanghai, China). Tween-80 and PEG-400 were purchased from Sangon Biotech (Shanghai, China). Anti-PPAR-α antibody (#ab24509) and anti-CD68 antibody (#ab125212) were obtained from Abcam (Shanghai, China). Anti-caspase-1 antibody (clone 14F468) was purchased from Santa Cruz (Shanghai, China). Anti-GAPDH antibody (clone 1E6D9) was purchased from Proteintech (Wuhan, China). Anti-NLRP3 antibody (#A5652) was acquired from ABclonal Technology (Wuhan, China). Anti-α-SMA antibody (clone 1A4) and anti-LC3B antibody (L7543) were obtained from Sigma-Aldrich (Shanghai, China). Antibodies against p62 (#A19700), Beclin1 (#A11761), and ATG7 (#A0691) were obtained from ABconal (Wuhan, China). Horseradish peroxidase (HRP)-conjugated goat anti-mouse and goat anti-rabbit immunoglobulin G (IgG) were purchased from Proteintech (Wuhan, China).

For all in vitro experiments, ML604440 (Probechem, PC-60968), ONX -0914 (MCE, HY-13207) were dissolved at a concentration of 10 mM in DMSO and stored at −80°C. A final DMSO concentration of 0.3% was used. For proteasome inhibition in mice, ML604440 was diluted in PBS with 5% polyethylene glycol (PEG-400; Sangon Biotech) and 1% Tween-80 (Sangon Biotech) immediately before use. ONX 0914 was formulated in an aqueous solution of 10% (w/v) sulfobutylether-beta-cyclodextrin and 10 mM sodium citrate (pH 6) and administered to mice as a subcutaneous bolus dose of 10 mg/kg.