Fig. 6: Genetic inhibition of CYP2E1 or ADRB increases perivenous KC survival and ALI.

a Experiment 1 (Inhibition of hepatic metabolism): Hepatic CYP2E1 wild-type (+/+) and heterozygous KO (+/−) mice were fed an EtOH diet for 6 weeks (n = 4/group; 3 biological replicates). Experiment 2 (Inhibition of catecholamine receptors): ADRB1/2 wild-type (+/+) and double KO (−/−) mice were fed an EtOH diet for 8 weeks (n = 5/group; 3 biological replicates). b Portal catecholamine levels were measured. c Serum GDF15, ALT, and AST levels were measured. d Representative immunoblots for ADRB2, PKA-Cα, GDF15, and mitochondrial CYP2E1 (2 blots/group). e qRT‒PCR analyses of whole liver tissues (n = 3/group). Not detected (n.d.). f Representative CYP2E1 and CLEC4F immunostaining with the average number of CLEC4F⁺ KCs in the CYP2E1⁺ perivenous area. Scale bars, 50 µm. g, h Flow cytometry analyses of hepatic Ly6G⁺CD11b⁺ neutrophils, F4/80^lowCD11b⁺ macrophages, F4/80^lowLy6C^high macrophages, and F4/80^lowLy6C^low macrophages. Data are presented as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 by Student’s t test. The illustration in Fig. 6a was created with BioRender.com.