Fig. 7: Bromodomain inhibitor UMN627 attenuates liver CXCL production and neutrophil infiltration in an alcohol binge/LPS model.

a Schematic of alcohol binge/LPS model protocol. Mice underwent once-daily gastric gavage with alcohol or maltose dextran for 3 days. A subset of mice also received IP injection of UMN627. Alcohol-gavaged mice also received IP injection of LPS on day 4, 8 h before sacrifice (n = 7 Control/Veh, n = 10 Binge + LPS/Veh, n = 7 Control/UMN627, n = 12 Binge+LPS/UMN627, same n for remaining panels of this figure). b qPCRs demonstrated CXCL chemokine and neutrophil marker Ly6g expression elevation with alcohol/LPS treatment. This response was attenuated by UMN627. Expression levels were normalized to the average expression of maltose gavaged control mice. c IHC for MPO is shown, with a number of neutrophils per low power field on the y-axis. The experiment was repeated with similar results. d Frozen section of mouse liver was stained with BODIPY 493/503 (green) and DAPI was used to stain nuclei (blue). The experiment was repeated with similar results. e Serum ALT levels did not show statistical differences among various groups. For all analyses, two-way ANOVA was performed on normalized expression values for qPCRs, cell counts for IHC staining, normalized quantification of BODIPY 493/503 staining, or ALT values, with post hoc Tukey’s multiple comparison correction. Data represented as mean ± SD.