Hypoxia-Inducible Factor-2α Reprograms Liver Macrophages to Protect Against Acute Liver Injury Through the Production of Interleukin-6.

ABSTRACT:

Background and aims

Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure, resulting in death or liver transplantation in more than one third of patients in the United States. The effectiveness of the only antidote, N-acetylcysteine, declines rapidly after APAP ingestion, long before patients are admitted to the clinic with symptoms of severe liver injury. The direct hepatotoxicity of APAP triggers a cascade of innate immune responses that may exacerbate or limit the progression of tissue damage. A better understanding of this complex mechanism will help uncover targets for therapeutic interventions.

Approach and results

We observed that APAP challenge caused stabilization of hypoxia-inducible factors (HIFs) in the liver and hepatic macropha

SUBMITTER: Gao RY 

PROVIDER: S-EPMC7075728 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature