Related Experiment Video
Updated: Aug 26, 2025
06:47
Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
7.2K
Macrophage malfunction in Triptolide-induced indirect hepatotoxicity
Tingting Qin1,2,3,4, Muhammad Hasnat5, Yang Zhou6
1Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Frontiers in Pharmacology
|October 13, 2022
Summary
Triptolide (TP) exacerbates liver injury by altering macrophage function, increasing inflammation, and reducing phagocytosis. Depleting macrophages alleviates this indirect hepatotoxicity, suggesting MerTK as a potential TP target.
Area of Science:
- Immunology
- Hepatology
- Pharmacology
Background:
- Indirect hepatotoxicity mechanisms remain unclear.
- Triptolide (TP) causes indirect hepatotoxicity via hepatocyte dysfunction.
- The role of immune cells, particularly macrophages, in TP-induced hepatotoxicity requires investigation.
Purpose of the Study:
- To explore the involvement of macrophages in TP-induced indirect hepatotoxicity.
- To elucidate how macrophages modulate liver hypersensitivity to lipopolysaccharide (LPS) after TP exposure.
Main Methods:
- Mice were treated with TP and LPS; serum markers and macrophage phenotypes were analyzed.
- Macrophage depletion using clodronate liposomes assessed their role in liver injury.
- Macrophage inflammatory cytokine secretion and phagocytosis were measured.
- Reverse docking identified MerTK as a potential TP target on macrophages.
Main Results:
- TP pretreatment sensitized livers to LPS, recruiting M1-polarized macrophages.
- Macrophage depletion significantly reduced TP/LPS-induced liver injury.
- TP impaired macrophage inflammatory profiles and phagocytic capacity.
- MerTK was identified as a potential target of TP.
Conclusions:
- TP disrupts hepatic macrophage function, increasing inflammation and endotoxin accumulation, leading to indirect hepatotoxicity.
- MerTK is a potential molecular target of TP in macrophages, warranting further in vivo and in vitro validation.
