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

Simon R. Carlile; Jenna Shiels; Lauren Kerrigan; Rebecca Delaney; Julianne Megaw; Brendan F. Gilmore; Sinead Weldon; John P. Dalton; Clifford C. Taggart

doi:10.1038/s41598-019-42537-8

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

Simon R. Carlile, Jenna Shiels, Lauren Kerrigan, Rebecca Delaney, Julianne Megaw, Brendan F. Gilmore, Sinead Weldon, John P. Dalton, Clifford C. Taggart

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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 language	English
Article number	6071
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-42537-8
Publication status	Published - 15 Apr 2019

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Sea snake cathelicidin (Hc-cath) exerts a protective efect in mouse models of lung infammation and infection
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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.}",

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

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