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Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate

The toxicity of available drugs for treatment of leishmaniasis, coupled with emerging drug resistance, make it urgent to find new therapies. Antimicrobial peptides (AMPs) have a strong broad-spectrum antimicrobial activity with distinctive modes of action and are considered as promising therapeutic...

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Autores principales: Dabirian, Sara, Taslimi, Yasaman, Zahedifard, Farnaz, Gholami, Elham, Doustdari, Fatemeh, Motamedirad, Mahdieh, Khatami, Shohreh, Azadmanesh, Kayhan, Nylen, Susanne, Rafati, Sima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798388/
https://www.ncbi.nlm.nih.gov/pubmed/24147170
http://dx.doi.org/10.1371/journal.pntd.0002491
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author Dabirian, Sara
Taslimi, Yasaman
Zahedifard, Farnaz
Gholami, Elham
Doustdari, Fatemeh
Motamedirad, Mahdieh
Khatami, Shohreh
Azadmanesh, Kayhan
Nylen, Susanne
Rafati, Sima
author_facet Dabirian, Sara
Taslimi, Yasaman
Zahedifard, Farnaz
Gholami, Elham
Doustdari, Fatemeh
Motamedirad, Mahdieh
Khatami, Shohreh
Azadmanesh, Kayhan
Nylen, Susanne
Rafati, Sima
author_sort Dabirian, Sara
collection PubMed
description The toxicity of available drugs for treatment of leishmaniasis, coupled with emerging drug resistance, make it urgent to find new therapies. Antimicrobial peptides (AMPs) have a strong broad-spectrum antimicrobial activity with distinctive modes of action and are considered as promising therapeutic agents. The defensins, members of the large family of AMPs, are immunomodulatory molecules and important components of innate immune system. Human neutrophil peptide-1 (HNP-1), which is produced by neutrophils, is one of the most potent defensins. In this study, we described anti-parasitic activity of recombinant HNP-1 (rHNP-1) against Leishmania major promastigotes and amastigotes. Furthermore, we evaluated the immunomodulatory effect of rHNP-1 on parasite-infected neutrophils and how neutrophil apoptosis was affected. Our result showed that neutrophils isolated from healthy individuals were significantly delayed in the onset of apoptosis following rHNP-1 treatment. Moreover, there was a noteworthy increase in dying cells in rHNP-1- and/or CpG–treated neutrophils in comparison with untreated cells. There is a considerable increase in TNF-α production from rHNP-1-treated neutrophils and decreased level of TGF-β concentration, a response that should potentiate the immune system against parasite invasion. In addition, by using real-time polymerase chain reaction (real-time PCR), we showed that in vitro infectivity of Leishmania into neutrophils is significantly reduced following rHNP-1 treatment compared to untreated cells.
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spelling pubmed-37983882013-10-21 Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate Dabirian, Sara Taslimi, Yasaman Zahedifard, Farnaz Gholami, Elham Doustdari, Fatemeh Motamedirad, Mahdieh Khatami, Shohreh Azadmanesh, Kayhan Nylen, Susanne Rafati, Sima PLoS Negl Trop Dis Research Article The toxicity of available drugs for treatment of leishmaniasis, coupled with emerging drug resistance, make it urgent to find new therapies. Antimicrobial peptides (AMPs) have a strong broad-spectrum antimicrobial activity with distinctive modes of action and are considered as promising therapeutic agents. The defensins, members of the large family of AMPs, are immunomodulatory molecules and important components of innate immune system. Human neutrophil peptide-1 (HNP-1), which is produced by neutrophils, is one of the most potent defensins. In this study, we described anti-parasitic activity of recombinant HNP-1 (rHNP-1) against Leishmania major promastigotes and amastigotes. Furthermore, we evaluated the immunomodulatory effect of rHNP-1 on parasite-infected neutrophils and how neutrophil apoptosis was affected. Our result showed that neutrophils isolated from healthy individuals were significantly delayed in the onset of apoptosis following rHNP-1 treatment. Moreover, there was a noteworthy increase in dying cells in rHNP-1- and/or CpG–treated neutrophils in comparison with untreated cells. There is a considerable increase in TNF-α production from rHNP-1-treated neutrophils and decreased level of TGF-β concentration, a response that should potentiate the immune system against parasite invasion. In addition, by using real-time polymerase chain reaction (real-time PCR), we showed that in vitro infectivity of Leishmania into neutrophils is significantly reduced following rHNP-1 treatment compared to untreated cells. Public Library of Science 2013-10-17 /pmc/articles/PMC3798388/ /pubmed/24147170 http://dx.doi.org/10.1371/journal.pntd.0002491 Text en © 2013 Dabirian et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dabirian, Sara
Taslimi, Yasaman
Zahedifard, Farnaz
Gholami, Elham
Doustdari, Fatemeh
Motamedirad, Mahdieh
Khatami, Shohreh
Azadmanesh, Kayhan
Nylen, Susanne
Rafati, Sima
Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate
title Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate
title_full Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate
title_fullStr Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate
title_full_unstemmed Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate
title_short Human Neutrophil Peptide-1 (HNP-1): A New Anti-Leishmanial Drug Candidate
title_sort human neutrophil peptide-1 (hnp-1): a new anti-leishmanial drug candidate
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798388/
https://www.ncbi.nlm.nih.gov/pubmed/24147170
http://dx.doi.org/10.1371/journal.pntd.0002491
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