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Updated: Jul 17, 2026
In vitro Measurements of Tracheal Constriction Using Mice
Published on: June 25, 2012
Human β-defensin-3 induces IL-8 release and apoptosis in airway smooth muscle cells
1Center for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Background:
Human airway smooth muscle cells (ASMCs) may have a pro-inflammatory role through the release of inflammatory mediators. Increasing evidence indicates that human β-defensins (HBDs) are related to pathogenesis of asthma.
Objectives:
To examine the plasma level of HBD-1, HBD-2 and HBD-3 in asthmatic patients and the expression of their mouse orthologues in the lung tissue of a mouse model of chronic severe asthma. Further to investigate the effect of HBD-3 on the release of the pro-inflammatory cytokine IL-8 and to explore the mechanisms.
Methods:
The plasma levels of HBD-1, HBD-2 and HBD-3 from 34 healthy controls and 25 asthmatic patients were determined by ELISA. The expression of mouse β-defensins MBD-1, MBD-3 and MBD-14 in the lung tissue of asthmatic mice was detected by Western blot. The ASMCs were cultured with HBD-3 for 24 hour, and then the supernatant level of IL-8 was evaluated by ELISA and the cell viability was examined by WST-1 assay. The signalling pathway was investigated with blocking antibodies or pharmacological inhibitors.
Results:
The plasma levels of HBD-1 and HBD-3 were elevated in asthmatic patients, and the expression of MBD-14, the mouse orthologue for HBD-3, was increased in asthmatic mice. HBD-3-induced IL-8 production in a CCR6 receptor-specific manner and was dependent on multiple signalling pathways. Moreover, HBD-3-induced cell apoptosis concurrently, which was dependent on the ERK1/2 MAPK pathway. Mitochondrial ROS regulated both HBD-3-induced IL-8 production and cell apoptosis.
Conclusions And Clinical Relevance:
These observations provide clear evidence of an important new mechanism for the promotion of airway inflammation and tissue remodelling with potential relevance for the treatment of asthma.
Insights
Human β-defensins (HBDs) like HBD-1 and HBD-3 are elevated in asthma, promoting airway inflammation and apoptosis via IL-8 and the ERK1/2 MAPK pathway. This reveals a new mechanism for asthma treatment.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- Human airway smooth muscle cells (ASMCs) contribute to airway inflammation.
- Human β-defensins (HBDs) are increasingly implicated in asthma pathogenesis.
Purpose of the Study:
- To measure plasma levels of HBD-1, HBD-2, and HBD-3 in asthmatics.
- To assess mouse orthologue expression in a mouse asthma model.
- To investigate HBD-3's effect on IL-8 release and underlying mechanisms.
Main Methods:
- ELISA for plasma HBD levels in humans.
- Western blot for mouse β-defensin expression in lung tissue.
- ASMC culture to study HBD-3 effects on IL-8, cell viability, and signaling pathways.
Main Results:
- Elevated plasma HBD-1 and HBD-3 in asthmatics; increased MBD-14 (HBD-3 orthologue) in mouse lungs.
- HBD-3 induced IL-8 release via CCR6 and multiple signaling pathways.
- HBD-3 triggered apoptosis dependent on ERK1/2 MAPK and mitochondrial ROS.
Conclusions:
- HBD-3 promotes airway inflammation and apoptosis through specific signaling pathways.
- These findings elucidate a novel mechanism in asthma pathogenesis.
- This offers potential therapeutic targets for asthma treatment.
