Notch Signaling Aggravates Helicobacter pylori-Induced Inflammation by Promoting Macrophage Activation and
Yunxuan He1, Danli Xiao1, Hongfei Zhu1
1School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
The American Journal of Pathology
|May 2, 2025
Summary
Notch signaling exacerbates Helicobacter pylori infection by activating macrophages and T cell responses. Inhibiting Notch signaling with DAPT reduced inflammation and improved gastric mucosal cell apoptosis in mice.
Area of Science:
- Immunology
- Gastroenterology
- Cellular Biology
Background:
- Notch signaling regulates immune responses in various diseases.
- Its precise role in Helicobacter pylori infection remains unclear.
Purpose of the Study:
- To investigate the role of Notch signaling in H. pylori infection.
- To explore Notch signaling as a potential therapeutic target.
Main Methods:
- In vitro studies using murine bone marrow-derived macrophages and CD4+ T cells.
- Real-time quantitative PCR, Western blot, and flow cytometry.
- In vivo studies in H. pylori-infected mice treated with a Notch inhibitor (DAPT).
Main Results:
- H. pylori activates Notch signaling via Jagged-1 in macrophages and T cells.
- Notch signaling reciprocally enhances the NF-κB pathway.
- DAPT treatment reduced inflammatory mediators, modulated macrophage phenotype, inhibited Th1/Th17 differentiation, decreased gastric inflammation, and improved cell apoptosis.
Conclusions:
- Notch signaling exacerbates H. pylori-induced inflammation by promoting macrophage activation and Th1/Th17 responses.
- Targeting Notch signaling may offer a therapeutic strategy for H. pylori-related diseases.
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