IL-17 deficiency attenuates acetaminophen-induced hepatotoxicity in mice

Hung Chen Lee, Chia Chih Liao, Yuan Ji Day, Jiin Tarng Liou, Allen H. Li, Fu Chao Liu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

27 Scopus citations

Abstract

Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), hepatocyte necrosis, and cell death, and leads to acute liver failure. Interleukin-17 (IL-17), a pro-inflammatory cytokine, plays a key role in the recruitment of neutrophils into sites of inflammation and subsequent damage after liver ischemia-reperfusion injury. In this study, we employed IL-17 knockout (KO) mice to investigate the role of IL-17 in APAP-induced hepatotoxicity. IL-17 wide type (WT) and IL-17 KO mice received an intraperitoneal injection of APAP (300 mg/kg). After 16 h of treatment, the hepatic injury, inflammatory mediators, immune cell infiltration, and western blotting were examined and analyzed. The serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity were significantly elevated 16 h after APAP treatment in the WT mice. IL-17 deficiency significantly attenuates APAP-induced liver injury, MPO activity, pro-inflammatory cytokines (tumor necrosis factor-α, IL-6 and interferon-γ) levels and inflammatory cell (neutrophils, macrophage) infiltration in the liver. Moreover, phosphorylated extracellular signal-regulated kinase (ERK) was significantly decreased at 16 h after APAP treatment in the IL-17 KO mice compared with the IL-17 WT mice. Our data suggests that IL-17 plays a pivotal role in APAP-induced hepatotoxicity through modulation of inflammatory response, and perhaps in part through the ERK signaling pathway. Blockade of IL-17 could be a potential therapeutic target for APAP-induced hepatotoxicity.

Original languageEnglish
Pages (from-to)20-30
Number of pages11
JournalToxicology Letters
Volume292
DOIs
StatePublished - 08 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • Acetaminophen
  • ERK
  • Hepatotoxicity
  • IL-17

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