Sea snake cathelicidin (Hc-cath) exerts a protective effect in mouse models of lung inflammation and infection
Sea snake cathelicidin (Hc-cath) exerts a protective effect in mouse models of lung inflammation and infection
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DOI：
10.1038/s41598-019-42537-8
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发表时间：
2019-04-15
影响因子：
4.6
通讯作者：
Taggart, Clifford C.
中科院分区：
文献类型：
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作者：
Carlile, Simon R.;Shiels, Jenna;Taggart, Clifford C.
我们利用体内炎症和感染模型研究了 Hc-cath 的抗炎和抗菌活性，Hc-cath 是一种源自海蛇 Hydrophisyanocyntus 毒液的抗菌素肽。在体外、蜡蛾、大蜡螟体内以及腹膜内和呼吸道铜绿假单胞菌感染的小鼠模型中评估了 Hc-cath 功能。 Hc-Cath 下调巨噬细胞中 LPS 诱导的促炎反应，并在 5 天的时间内显着提高铜绿假单胞菌感染大蜡螟的存活率。我们还首次证明，Hc-cath 可以通过显着减少促炎细胞因子和中性粒细胞趋化剂 KC 的释放，从而减少肺部细胞浸润，从而调节 LPS 诱导的肺部炎症小鼠模型中的炎症。此外，Hc-cath 治疗显着降低了铜绿假单胞菌腹膜内和呼吸道感染小鼠模型中的细菌负荷和炎症。 Hc-cath 在我们的研究中的作用凸显了开发这种肽作为治疗开发候选肽的潜力。
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.