Neutrophil elastase increases MUC4 expression in normal human bronchial epithelial cells.

Journal Article (Journal Article)

In chronic obstructive pulmonary diseases, the airway epithelium is chronically exposed to neutrophil elastase, an inflammatory protease. The cellular response to neutrophil elastase dictates the balance between epithelial injury and repair. Key regulators of epithelial migration and proliferation are the ErbB receptor tyrosine kinases, including the epidermal growth factor receptor. In this context, we investigated whether neutrophil elastase may regulate expression of MUC4, a membrane-tethered mucin that has recently been identified as a ligand for ErbB2, the major heterodimerization partner of the epidermal growth factor receptor. In normal human bronchial epithelial cells, neutrophil elastase increased MUC4 mRNA levels in both a concentration- and time-dependent manner. RNA stability assays revealed that neutrophil elastase increased MUC4 mRNA levels by prolonging the mRNA half-life from 5 to 21 h. Neutrophil elastase also increased MUC4 glycoprotein levels as determined by Western analysis, using a monoclonal antibody specific for a nontandem repeat MUC4 sequence. Therefore, airway epithelial cells respond to neutrophil elastase exposure by increasing expression of MUC4, a potential activator of epithelial repair mechanisms.

Full Text

Duke Authors

Cited Authors

  • Fischer, BM; Cuellar, JG; Diehl, ML; deFreytas, AM; Zhang, J; Carraway, KL; Voynow, JA

Published Date

  • April 2003

Published In

Volume / Issue

  • 284 / 4

Start / End Page

  • L671 - L679

PubMed ID

  • 12495942

International Standard Serial Number (ISSN)

  • 1040-0605

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00220.2002


  • eng

Conference Location

  • United States