Sex-Specific Regulation of Interferon-γ Cytotoxicity in Mouse Liver by Autophagy.

ABSTRACT:

Background and aims

Interferon-γ (IFNγ) is a central activator of immune responses in the liver and other organs. IFNγ triggers tissue injury and inflammation in immune diseases, which occur predominantly in females for unknown reasons. Recent findings that autophagy regulates hepatotoxicity from proinflammatory cytokines led to an examination of whether defective hepatocyte autophagy underlies sex-specific liver injury and inflammation induced by IFNγ.

Approach and results

A lentiviral autophagy-related 5 (Atg5) knockdown was performed to decrease autophagy-sensitized alpha mouse liver (AML 12) hepatocytes to death from IFNγ in combination with IL-1β or TNF. Death was necrosis attributable to impaired energy homeostasis and adenosine triphosphate depletion. Male mice with d

SUBMITTER: Shen Y 

PROVIDER: S-EPMC8542567 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature