Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line.
AUTOR(ES)
Nakamura, H
RESUMO
The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by epithelial cells, thus recruiting neutrophils to the airways. BET-1A human bronchial epithelial cells at rest or incubated with normal ELF showed little IL-8 gene expression, but after incubation with CF ELF, a marked increase in IL-8 transcript levels was observed. CF ELF contained high levels of neutrophil elastase (NE) and various serine protease inhibitors prevented CF ELF from inducing IL-8 gene expression in BET-1A cells, suggesting that NE was the dominant inducer for IL-8 production in CF ELF. The addition of purified NE caused BET-1A cells to increase IL-8 gene transcription with accumulation of mRNA transcripts and to release IL-8-like neutrophil chemotactic activity. These observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced the bronchial epithelium to secrete IL-8, which in turn recruits additional neutrophils to the bronchial surface.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=443018Documentos Relacionados
- Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung.
- Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis.
- A cystic fibrosis pancreatic adenocarcinoma cell line.
- Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line, THP-1, through acting concurrently on AP-1- and NF-kappaB-binding sites of the interleukin-8 gene.
- Yersinia enterocolitica Adhesin A Induces Production of Interleukin-8 in Epithelial Cells