Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease
| Autor: | Austin F. Dohrman, Marianne Gallup, Susumu Miyata, Jay A. Nadel, Alice Prince, Jian Dong Li, James R. Gum, Young S. Kim, Carol Basbaum |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Lipopolysaccharides
Transcriptional Activation Cystic Fibrosis Molecular Sequence Data Cystic Fibrosis Transmembrane Conductance Regulator Bronchi Mucin 2 Biology medicine.disease_cause Benzylidene Compounds Cystic fibrosis Epithelium Cell Line Microbiology Pathogenesis Nitriles medicine Humans RNA Messenger Enzyme Inhibitors Mucin-2 Multidisciplinary Pseudomonas aeruginosa Mucin Mucins Protein-Tyrosine Kinases Tyrphostins Biological Sciences medicine.disease Mucus Cystic fibrosis transmembrane conductance regulator Immunology biology.protein Tyrosine kinase |
| Zdroj: | Proceedings of the National Academy of Sciences. 94:967-972 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.94.3.967 |
| Popis: | An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a Cl ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly up-regulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyrphostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease. |
| Databáze: | OpenAIRE |
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