Study summary · research use only
The human cathelicidin LL-37 preferentially promotes apoptosis of infected airway epithelium
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this human cell study, the authors examined the cathelicidin LL-37 on infected airway epithelium. They describe LL-37 as an important cationic host defense peptide up-regulated in infection and inflammation in the human lung, previously shown to enhance pulmonary clearance of Pseudomonas aeruginosa in vivo. The abstract reports that at physiologically relevant concentrations, LL-37 preferentially promoted apoptosis of infected airway epithelium via enhanced mitochondrial membrane depolarization and cytochrome c release, with activation of caspase-9 and caspase-3, occurring only in the presence of both peptide and bacteria. This synergistic apoptosis in infected cells was caspase-dependent, contrasting with caspase-independent death from supraphysiologic peptide alone, and required whole, live bacteria and bacterial invasion. The authors propose LL-37-mediated apoptosis of infected airway cells as a novel inflammomodulatory role promoting clearance of respiratory pathogens.
Abstract
Cationic host defense peptides are key, evolutionarily conserved components of the innate immune system. The human cathelicidin LL-37 is an important cationic host defense peptide up-regulated in infection and inflammation, specifically in the human lung, and was shown to enhance the pulmonary clearance of the opportunistic pathogen Pseudomonas aeruginosa in vivo by as yet undefined mechanisms. In addition to its direct microbicidal potential, LL-37 can modulate inflammation and immune mechanisms in host defense against infection, including the capacity to modulate cell death pathways. We demonstrate that at physiologically relevant concentrations of LL-37, this peptide preferentially promoted the apoptosis of infected airway epithelium, via enhanced LL-37-induced mitochondrial membrane depolarization and release of cytochrome c, with activation of caspase-9 and caspase-3 and induction of apoptosis, which only occurred in the presence of both peptide and bacteria, but not with either stimulus alone. This synergistic induction of apoptosis in infected cells was caspase-dependent, contrasting with the caspase-independent cell death induced by supraphysiologic levels of peptide alone. We demonstrate that the synergistic induction of apoptosis by LL-37 and Pseudomonas aeruginosa required specific bacteria-epithelial cell interactions with whole, live bacteria, and bacterial invasion of the epithelial cell. We propose that the LL-37-mediated apoptosis of infected, compromised airway epithelial cells may represent a novel inflammomodulatory role for this peptide in innate host defense, promoting the clearance of respiratory pathogens.
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