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Chi3l1 regulates APAP-induced liver injury by promoting macrophage infiltration

Y Wang1, M Zhong, W Wang

  • 1Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, China. 43790964@qq.com.

European Review for Medical and Pharmacological Sciences
|June 19, 2019
PubMed
Abstract

Insights

Chitinase-3-like protein 1 (Chi3l1) protects against acetaminophen-induced liver injury by reducing inflammation and immune cell infiltration. Chi3l1 deficiency exacerbates liver damage, highlighting its protective role.

Area of Science:

  • Hepatology
  • Immunology
  • Toxicology

Background:

  • Acetaminophen (APAP) overdose is a leading cause of acute liver injury.
  • The role of Chitinase-3-like protein 1 (Chi3l1) in APAP-induced liver injury (APAP-ALI) is not fully understood.

Purpose of the Study:

  • To investigate the protective role of Chi3l1 in APAP-induced liver injury.
  • To elucidate the mechanisms by which Chi3l1 influences liver inflammation and injury.

Main Methods:

  • Established APAP-induced liver injury model in wild-type (WT) and Chi3l1-deficient (Chi3l1-/-) mice.
  • Assessed liver injury markers (ALT, apoptosis, histology), inflammatory cytokine levels (ELISA), and immune cell infiltration (flow cytometry).
  • Isolated bone marrow-derived macrophages (BMDMs) to evaluate inflammatory responses.

Main Results:

  • Chi3l1-/- mice exhibited significantly more severe liver injury, higher ALT levels, and increased apoptosis compared to WT mice after APAP administration.
  • Chi3l1 deficiency led to elevated levels of pro-inflammatory cytokines (MCP-1, IL-6) and increased infiltration of macrophages and neutrophils in the liver.
  • BMDMs from Chi3l1-/- mice promoted higher inflammatory cytokine expression.

Conclusions:

  • Chi3l1 plays a crucial protective role in mitigating APAP-induced liver injury.
  • Chi3l1 exerts its protective effects by inhibiting inflammatory cytokine secretion and reducing macrophage infiltration.
  • Targeting Chi3l1 may offer a therapeutic strategy for managing APAP-induced liver damage.

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