title: Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential.
abstract: Host defence peptides (HDPs) are short, cationic amphipathic peptides that play a key role in the response to infection and inflammation in all complex life forms. It is increasingly emerging that HDPs generally have a modest direct activity against a broad range of microorganisms, and that their anti-infective properties are mainly due to their ability to modulate the immune response. Here, we report the recombinant production and characterization of two novel HDPs identified in human Apolipoprotein B (residues 887-922) by using a bioinformatics method recently developed by our group. We focused our attention on two variants of the identified HDP, here named r(P)ApoBLand r(P)ApoBS, 38- and 26-residue long, respectively. Both HDPs were found to be endowed with a broad-spectrum antimicrobial activity while they show neither toxic nor haemolytic effects towards eukaryotic cells. Interestingly, both HDPs were found to display a significant anti-biofilm activity, and to act in synergy with either commonly used antibiotics or EDTA. The latter was selected for its ability to affect bacterial outer membrane permeability, and to sensitize bacteria to several antibiotics. Circular dichroism analyses showed that SDS, TFE, and LPS significantly alter r(P)ApoBLconformation, whereas slighter or no significant effects were detected in the case of r(P)ApoBSpeptide. Interestingly, both ApoB derived peptides were found to elicit anti-inflammatory effects, being able to mitigate the production of pro-inflammatory interleukin-6 and nitric oxide in LPS induced murine macrophages. It should also be emphasized that r(P)ApoBLpeptide was found to play a role in human keratinocytes wound closure in vitro. Altogether, these findings open interesting perspectives on the therapeutic use of the herein identified HDPs.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy; Department of Infectious Diseases and Immunology, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rosa
authors.initials: R
authors.lastname: Gaglione
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Dell'Olmo
authors.affiliation: Department of Infectious Diseases and Immunology, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bosso
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chino
authors.affiliation: Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Pane
authors.affiliation: Department of Chemical, Materials and Production Engineering, University of Naples Federico II, 80125 Naples, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Ascione
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Itri
authors.affiliation: Department of Chemical, Materials and Production Engineering, University of Naples Federico II, 80125 Naples, Italy; CEINGE Biotecnologie Avanzate, Via Sergio Pansini, 5, 80131 Naples, Italy; Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), UdR INSTM Napoli Federico II, P.le Tecchio, 80, 80125 Naples, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Caserta
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Amoresano
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Lombardi
authors.affiliation: Department of Infectious Diseases and Immunology, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Henk P
authors.initials: HP
authors.lastname: Haagsman
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy; Istituto Nazionale di Biostrutture e Biosistemi (INBB), Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Piccoli
authors.affiliation: Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Pizzo
authors.affiliation: Department of Infectious Diseases and Immunology, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Edwin J A
authors.initials: EJA
authors.lastname: Veldhuizen
authors.affiliation: Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Notomista
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy; Istituto Nazionale di Biostrutture e Biosistemi (INBB), Italy. Electronic address: anarciel@unina.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Arciello
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001055:Apolipoproteins B / Q000737:chemistry* / Q000627:therapeutic use; D002942:Circular Dichroism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use; D013056:Spectrophotometry, Ultraviolet
chemical_list: D001055:Apolipoproteins B; D010446:Peptide Fragments; D011994:Recombinant Proteins
keywords: Apolipoprotein B; Bacterial biofilm; Biocompatibility; Combination therapy; Host defence peptides; Immunomodulation; Lipopolysaccharide; Wound healing