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Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease

By Jian-Dong Li, Austin F. Dohrman, Marianne Gallup, Susumu Miyata, James R. Gum, Young S. Kim, Jay A. Nadel, Alice Prince and Carol B. Basbaum

Abstract

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

Topics: Biological Sciences
Publisher: The National Academy of Sciences of the USA
Year: 1997
OAI identifier: oai:pubmedcentral.nih.gov:19623
Provided by: PubMed Central
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