Neutrophil elastase-SERPINB1 axis in epithelial responses: Cell death, inflammation and SERPINB1 dynamics

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Molecular Biology

Background:

• Chronic inflammatory lung diseases involve elevated neutrophil elastase (NE), causing epithelial damage.
• Mechanisms of NE-induced disruption of epithelial anti-protease defenses, particularly SERPINB1 regulation, are poorly understood.

Purpose of the Study:

• To investigate NE-induced responses in bronchial epithelial cells at the air-liquid interface (ALI).
• Focus on epithelial cell death, inflammation, and SERPINB1 dynamics following NE exposure.

Main Methods:

• Bronchial epithelial cells cultured at ALI were exposed to varying NE concentrations and sides (apical/basolateral).
• Assessed cytotoxicity, apoptosis-related gene expression, cytokine secretion, and SERPINB1 levels (mRNA, protein, localization).
• Utilized siRNA-mediated SERPINB1 knockdown to confirm functional links.

Main Results:

• NE exposure caused dose- and time-dependent cytotoxicity and altered apoptosis-related gene expression.
• Cytokine release (IL-6, IL-8, GM-CSF) varied based on NE concentration, exposure side, and sampling compartment.
• SERPINB1 expression was significantly reduced, with altered localization, and its knockdown exacerbated NE-associated gene expression changes.

Conclusions:

• The NE-SERPINB1 axis is critical in determining epithelial cell fate, contributing to apoptosis and inflammation.
• NE disrupts epithelial anti-protease defenses, impacting protease-antiprotease balance in chronic airway inflammation.
• Findings support SERPINB1-modulating strategies to preserve epithelial integrity in lung diseases.