Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line.
TL;DR: Observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced theBronchial epithelium to secrete IL-8, which in turn recruits additional neutrophilia to the bronchia surface.
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Abstract: 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.
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Citations
Lung protease/anti-protease network and modulation of mucus production and surfactant activity
Ignacio Garcia-Verdugo,Delphyne Descamps,Delphyne Descamps,Michel Chignard,Michel Chignard,Lhousseine Touqui,Lhousseine Touqui,Jean-Michel Sallenave,Jean-Michel Sallenave +8 more
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46
Nebulised lipid-polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells.
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Transmigration of Human Neutrophils Across Airway Epithelial Cell Monolayers Is Preferentially in the Physiologic Basolateral-to-Apical Direction
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Neutrophil transmigration across monolayers of endothelial cells and airway epithelial cells is regulated by different mechanisms.
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45
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Ian Sabroe,Moira K. B. Whyte +1 more
TL;DR: The neutrophil is a crucial early defence against microbial infection, but neutrophilic inflammation can result in devastating acute and chronic inflammatory diseases.
45
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