Related Experiment Videos
Neutrophil elastase increases MUC4 expression in normal human bronchial epithelial cells
Bernard M Fischer1, Jacob G Cuellar, Meredith L Diehl
1Division of Pediatric Pulmonary Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
American Journal of Physiology. Lung Cellular and Molecular Physiology
|December 24, 2002
Summary
Neutrophil elastase, an inflammatory protease, increases MUC4 expression in airway epithelial cells. This response involves prolonged MUC4 mRNA stability, suggesting MUC4 may aid epithelial repair in chronic obstructive pulmonary diseases.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Molecular Biology
Background:
- Chronic obstructive pulmonary diseases (COPD) involve airway epithelial exposure to neutrophil elastase, an inflammatory protease.
- Epithelial cell response to neutrophil elastase influences tissue repair and injury.
- ErbB receptor tyrosine kinases, like the epidermal growth factor receptor, regulate epithelial cell migration and proliferation.
Purpose of the Study:
- To investigate if neutrophil elastase regulates MUC4 expression.
- To determine if MUC4, a mucin and ErbB2 ligand, is involved in the airway epithelial response to neutrophil elastase.
Main Methods:
- Normal human bronchial epithelial cells were treated with neutrophil elastase.
- MUC4 mRNA levels were quantified using concentration- and time-dependent assays.
- RNA stability assays were performed to assess mRNA half-life.
- MUC4 glycoprotein levels were analyzed via Western blot.
Main Results:
- Neutrophil elastase significantly increased MUC4 mRNA levels in a dose- and time-dependent manner.
- RNA stability assays showed neutrophil elastase prolonged MUC4 mRNA half-life from 5 to 21 hours.
- Western blot analysis confirmed increased MUC4 glycoprotein levels following neutrophil elastase exposure.
Conclusions:
- Airway epithelial cells increase MUC4 expression upon exposure to neutrophil elastase.
- This upregulation is mediated by increased MUC4 mRNA stability.
- Increased MUC4 expression represents a potential mechanism for epithelial repair activation in response to inflammatory stimuli.