Blood-derived macrophages prone to accumulate lysosomal lipids trigger oxLDL-dependent murine hepatic inflammation.

ABSTRACT: Despite the consistent rise of non-alcoholic steatohepatitis (NASH) worldwide, the mechanisms that govern the inflammatory aspect of this disease remain unknown. Previous research showed an association between hepatic inflammation and lysosomal lipid accumulation in blood-derived hepatic macrophages. Additionally, in vitro findings indicated that lipids, specifically derived from the oxidized low-density lipoprotein (oxLDL) particle, are resistant to removal from lysosomes. On this basis, we investigated whether lysosomal lipid accumulation in blood-derived hepatic macrophages is causally linked to hepatic inflammation and assessed to what extent increasing anti-oxLDL IgM autoantibodies can affect this mechanism. By creating a proof-of-concept mouse model, we demonstrate a causal role for

SUBMITTER: Houben T 

PROVIDER: S-EPMC5624963 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature