title: Human neutrophil peptide-1 (HNP-1): a new anti-leishmanial drug candidate.
abstract: 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.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Dabirian
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Taslimi
authors.forename: Farnaz
authors.initials: F
authors.lastname: Zahedifard
authors.forename: Elham
authors.initials: E
authors.lastname: Gholami
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Doustdari
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Motamedirad
authors.forename: Shohreh
authors.initials: S
authors.lastname: Khatami
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.forename: Susanne
authors.initials: S
authors.lastname: Nylen
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000328:Adult; D017209:Apoptosis; D002478:Cells, Cultured; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D018320:Leishmania major / Q000254:growth & development / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023084:alpha-Defensins / Q000494:pharmacology*
chemical_list: D007155:Immunologic Factors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D023084:alpha-Defensins; C406413:human neutrophil peptide 1