Lysosomal Cholesterol Hydrolysis Couples Efferocytosis to Anti-Inflammatory Oxysterol Production.

ABSTRACT:

Rationale

Macrophages face a substantial amount of cholesterol after the ingestion of apoptotic cells, and the LIPA (lysosomal acid lipase) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment.

Objective

Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo.

Methods and results

We show that LIPA inhibition causes a defective efferocytic response because of impaired generation of 25-hydroxycholesterol and 27-hydroxycholesterol. Reduced synthesis of 25-hydroxycholesterol after LIPA inhibition contributed to defective mitochondria-associated membrane leading to mitochondrial oxidative stress-induced NLRP3 (NOD-like receptor family, pyrin domain containing) inflammasome activation and cas

SUBMITTER: Viaud M 

PROVIDER: S-EPMC6034181 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature