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FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis

Sepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of F. multistriata. FM-CATH was found...

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Autores principales: Wu, Jiena, Zhang, Haiyun, Chen, Xiaoxin, Chai, Jinwei, Hu, Yunrui, Xiong, Weichen, Lu, Wancheng, Tian, Maolin, Chen, Xin, Xu, Xueqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415707/
https://www.ncbi.nlm.nih.gov/pubmed/34483941
http://dx.doi.org/10.3389/fphar.2021.731056
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author Wu, Jiena
Zhang, Haiyun
Chen, Xiaoxin
Chai, Jinwei
Hu, Yunrui
Xiong, Weichen
Lu, Wancheng
Tian, Maolin
Chen, Xin
Xu, Xueqing
author_facet Wu, Jiena
Zhang, Haiyun
Chen, Xiaoxin
Chai, Jinwei
Hu, Yunrui
Xiong, Weichen
Lu, Wancheng
Tian, Maolin
Chen, Xin
Xu, Xueqing
author_sort Wu, Jiena
collection PubMed
description Sepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of F. multistriata. FM-CATH was found to adopt an amphipathic α-helix structural in membrane-mimetic environments and possess favorable antimicrobial effects against bacteria and fungus. In addition, it triggered the agglutination of bacteria. It could also strongly bind to LPS and LTA. Additionally, FM-CATH affected the enzymatic activities of thrombin, plasmin, β-tryptase, and tPA, leading to coagulation inhibition in vitro and in vivo. Finally, we observed that FM-CATH improved survival rate and inhibited pathological alteration, bacterial count, serum biochemistry, and pro-inflammatory cytokine expression in the cecal ligation and puncture-induced sepsis mice. Taken together, these findings suggest that FM-CATH might be served as a promising agent for the treatment of sepsis.
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spelling pubmed-84157072021-09-04 FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis Wu, Jiena Zhang, Haiyun Chen, Xiaoxin Chai, Jinwei Hu, Yunrui Xiong, Weichen Lu, Wancheng Tian, Maolin Chen, Xin Xu, Xueqing Front Pharmacol Pharmacology Sepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of F. multistriata. FM-CATH was found to adopt an amphipathic α-helix structural in membrane-mimetic environments and possess favorable antimicrobial effects against bacteria and fungus. In addition, it triggered the agglutination of bacteria. It could also strongly bind to LPS and LTA. Additionally, FM-CATH affected the enzymatic activities of thrombin, plasmin, β-tryptase, and tPA, leading to coagulation inhibition in vitro and in vivo. Finally, we observed that FM-CATH improved survival rate and inhibited pathological alteration, bacterial count, serum biochemistry, and pro-inflammatory cytokine expression in the cecal ligation and puncture-induced sepsis mice. Taken together, these findings suggest that FM-CATH might be served as a promising agent for the treatment of sepsis. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415707/ /pubmed/34483941 http://dx.doi.org/10.3389/fphar.2021.731056 Text en Copyright © 2021 Wu, Zhang, Chen, Chai, Hu, Xiong, Lu, Tian, Chen and Xu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wu, Jiena
Zhang, Haiyun
Chen, Xiaoxin
Chai, Jinwei
Hu, Yunrui
Xiong, Weichen
Lu, Wancheng
Tian, Maolin
Chen, Xin
Xu, Xueqing
FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis
title FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis
title_full FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis
title_fullStr FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis
title_full_unstemmed FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis
title_short FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis
title_sort fm-cath, a novel cathelicidin from fejervarya multistriata, shows therapeutic potential for treatment of clp-induced sepsis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415707/
https://www.ncbi.nlm.nih.gov/pubmed/34483941
http://dx.doi.org/10.3389/fphar.2021.731056
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