Fig. 5: Genetic or pharmacologic inhibition of mGluR5 in Kupffer cells attenuates alcohol-related liver injury in mice.

a Measurement of serum ALT, AST, TG, and glutamate levels in KC^fl/fl and KC-specific mGluR5 knockout mice (KC^ΔGrm5) fed with 2-week EtOH plus binge drinking (n = 6/group). b Representative flow cytometry panels and bar graphs indicate frequencies of the neutrophils, macrophages, and eosinophils of liver MNCs from KC^ΔGrm5 mice compared to KC^fl/fl (n = 6/group). c Representative H & E and immunostaining of ALDH4A1 and CYP2E1 in liver sections from KC^fl/fl and KC^ΔGrm5 mice. Scale bar, 50 μm. d Relative mRNA expression of Cxcl1, Ccl2, Il1b, and Cybb in isolated KCs from KC^fl/fl and KC^ΔGrm5 mice (n = 4/group). e ROS generation in isolated KCs from KC^fl/fl and KC^ΔGrm5 mice (n = 4/group). f Protocol schematic of in vitro co-culture system of HEPs and KCs. Measurement of glutamate (n = 4/group) and LDH in co-culture media (n = 3/group). g Relative mRNA expression of Cxcl1 and Cybb in co-cultured KCs (n = 4/group). h Measurement of serum ALT, AST, TG, and glutamate levels following intraperitoneal injection of VEH or mGluR5 antagonist (MPEP; 10 mg/kg) for three consecutive days prior to sacrifice (n = 5/group). i Representative H&E stains in liver sections. Scale bar, 50 μm. j ROS generation in isolated KCs from VEH or MPEP-treated mice. k Relative mRNA expression related to inflammatory response in isolated KCs (n = 4/group) from MPEP-treated mice. Statistical comparisons were made using one-way ANOVA with Tukey’s multiple comparisons test (f) or two-tailed unpaired t-test (a, b, d, g, h, k). Data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001.