Sea snake cathelicidin (Hc-cath) exerts a protective effect in mouse models of lung inflammation and infection

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Abstract

We investigated the anti-inflammatory and antibacterial activities of Hc-cath, a cathelicidin peptide derived from the venom of the sea snake, Hydrophis cyanocyntus, using in vivo models of inflammation and infection. Hc-cath function was evaluated in in vitro, in vivo in the wax moth, Galleria mellonella, and in mouse models of intraperitoneal and respiratory Pseudomonas aeruginosa infection. Hc-Cath downregulated LPS-induced pro-inflammatory responses in macrophages and significantly improved the survival of P. aeruginosa infected G. mellonella over a 5-day period. We also demonstrated, for the first time, that Hc-cath can modulate inflammation in a mouse model of LPS-induced lung inflammation by significantly reducing the release of the pro-inflammatory cytokine and neutrophil chemoattractant, KC, resulting in reduced cellular infiltration into the lungs. Moreover, Hc-cath treatment significantly reduced the bacterial load and inflammation in mouse models of P. aeruginosa intraperitoneal and respiratory infection. The effect of Hc-cath in our studies highlights the potential to develop this peptide as a candidate for therapeutic development.
Original languageEnglish
Article number6071
Number of pages9
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 15 Apr 2019

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Elapidae
Pseudomonas aeruginosa
Pneumonia
Inflammation
Elapid Venoms
Infection
Pseudomonas Infections
Peptides
Moths
Bacterial Load
Waxes
Chemotactic Factors
Respiratory Tract Infections
Neutrophils
Anti-Inflammatory Agents
Down-Regulation
Macrophages
Cytokines
Lung
CAP18 lipopolysaccharide-binding protein

Cite this

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title = "Sea snake cathelicidin (Hc-cath) exerts a protective effect in mouse models of lung inflammation and infection",
abstract = "We investigated the anti-inflammatory and antibacterial activities of Hc-cath, a cathelicidin peptide derived from the venom of the sea snake, Hydrophis cyanocyntus, using in vivo models of inflammation and infection. Hc-cath function was evaluated in in vitro, in vivo in the wax moth, Galleria mellonella, and in mouse models of intraperitoneal and respiratory Pseudomonas aeruginosa infection. Hc-Cath downregulated LPS-induced pro-inflammatory responses in macrophages and significantly improved the survival of P. aeruginosa infected G. mellonella over a 5-day period. We also demonstrated, for the first time, that Hc-cath can modulate inflammation in a mouse model of LPS-induced lung inflammation by significantly reducing the release of the pro-inflammatory cytokine and neutrophil chemoattractant, KC, resulting in reduced cellular infiltration into the lungs. Moreover, Hc-cath treatment significantly reduced the bacterial load and inflammation in mouse models of P. aeruginosa intraperitoneal and respiratory infection. The effect of Hc-cath in our studies highlights the potential to develop this peptide as a candidate for therapeutic development.",
author = "Carlile, {Simon R.} and Jenna Shiels and Lauren Kerrigan and Rebecca Delaney and Julianne Megaw and Gilmore, {Brendan F.} and Sinead Weldon and Dalton, {John P.} and Taggart, {Clifford C.}",
year = "2019",
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AU - Shiels, Jenna

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AU - Delaney, Rebecca

AU - Megaw, Julianne

AU - Gilmore, Brendan F.

AU - Weldon, Sinead

AU - Dalton, John P.

AU - Taggart, Clifford C.

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AB - We investigated the anti-inflammatory and antibacterial activities of Hc-cath, a cathelicidin peptide derived from the venom of the sea snake, Hydrophis cyanocyntus, using in vivo models of inflammation and infection. Hc-cath function was evaluated in in vitro, in vivo in the wax moth, Galleria mellonella, and in mouse models of intraperitoneal and respiratory Pseudomonas aeruginosa infection. Hc-Cath downregulated LPS-induced pro-inflammatory responses in macrophages and significantly improved the survival of P. aeruginosa infected G. mellonella over a 5-day period. We also demonstrated, for the first time, that Hc-cath can modulate inflammation in a mouse model of LPS-induced lung inflammation by significantly reducing the release of the pro-inflammatory cytokine and neutrophil chemoattractant, KC, resulting in reduced cellular infiltration into the lungs. Moreover, Hc-cath treatment significantly reduced the bacterial load and inflammation in mouse models of P. aeruginosa intraperitoneal and respiratory infection. The effect of Hc-cath in our studies highlights the potential to develop this peptide as a candidate for therapeutic development.

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