FIGURE 7.

Model for the critical link between β-GluCer, β-glucosylceramide (β-GluCer) and the production of IL-1β-containing sEVs. Ethanol exposure results in the release of β-GlucCer from injury hepatocyte. Mincle, expressed by hepatic macrophages, senses β-GluCer and stimulates the release of IL-1β-containing sEVs in a GSDMD-dependent mechanism. The sEVs, in turn, interact with hepatocytes to stimulate the expression of the acute-phase protein SAA. The Mincle-GSDMD-IL-1β pathway provides a mechanism linking hepatocyte injury to inflammation to perpetuate chronic inflammation in alcohol-associated liver disease. Abbreviations: Mincle, macrophage-inducible C-type lectin; GSDMD, gasdermin D; sEVs, small extracellular vesicles.