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Restraint Stress-Induced Neutrophil Inflammation Contributes to Concurrent Gastrointestinal Injury in Mice
Rina Munalisa1, Te-Sheng Lien1, Ping-Yeh Tsai1
1Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan.
International Journal of Molecular Sciences
|May 25, 2024
Summary
Psychological stress harms the gut. Our study shows neutrophils cause this inflammation via NETosis, a cell death process. Inhibiting NETosis protected against stress-induced gastrointestinal injury.
Area of Science:
- Gastroenterology
- Immunology
- Stress Physiology
Background:
- Psychological stress is linked to gastrointestinal diseases.
- The precise mechanisms of stress-induced gut injury remain unclear.
Purpose of the Study:
- To investigate the mechanism of stress-induced gastrointestinal injury.
- To explore potential intervention strategies for this condition.
Main Methods:
- Utilized a restraint stress mouse model.
- Assessed gastrointestinal injury using Evans blue dye.
- Analyzed splenic leukocyte inflammatory status and cell death via flow cytometry.
Main Results:
- Neutrophils were identified as the key innate immune cells driving stress-induced inflammation.
- Stress elevated pro-inflammatory markers, reactive oxygen species, mitochondrial burden, and cell death in splenic neutrophils.
- NETosis was the predominant regulated cell death pathway, with neutrophil extracellular traps (NETs) implicated in the injury.
- Inhibition of NETosis with GSK484 ameliorated stress-induced NET release and gastrointestinal damage.
Conclusions:
- Neutrophil NETosis plays a critical role in psychological stress-induced gastrointestinal inflammation and injury.
- Targeting neutrophil NETosis presents a potential therapeutic strategy for managing stress-related gut disorders.

