title: A new cryptic cationic antimicrobial peptide from human apolipoprotein E with antibacterial activity and immunomodulatory effects on human cells.
abstract: Cationic antimicrobial peptides (AMPs) possess fast and broad-spectrum activity against both Gram-negative and Gram-positive bacteria, as well as fungi. It has become increasingly evident that many AMPs, including those that derive from fragments of host proteins, are multifunctional and able to mediate various immunomodulatory functions and angiogenesis. Among these, synthetic apolipoprotein-derived peptides are safe and well tolerated in humans and have emerged as promising candidates in the treatment of various inflammatory conditions. Here, we report the characterization of a new AMP corresponding to residues 133-150 of human apolipoprotein E. Our results show that this peptide, produced either by chemical synthesis or by recombinant techniques in Escherichia coli, possesses a broad-spectrum antibacterial activity. As shown for several other AMPs, ApoE (133-150) is structured in the presence of TFE and of membrane-mimicking agents, like SDS, or bacterial surface lipopolysaccharide (LPS), and an anionic polysaccharide, alginate, which mimics anionic capsular exo-polysaccharides of several pathogenic microorganisms. Noteworthy, ApoE (133-150) is not toxic toward several human cell lines and triggers a significant innate immune response, assessed either as decreased expression levels of proinflammatory cytokines in differentiated THP-1 monocytic cells or by the induction of chemokines released from PBMCs. This novel bioactive AMP also showed a significant anti-inflammatory effect on human keratinocytes, suggesting its potential use as a model for designing new immunomodulatory therapeutics.
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.|Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Katia
authors.initials: K
authors.lastname: Pane
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Sgambati
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Zanfardino
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Smaldone
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cafaro
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Angrisano
authors.affiliation: Institute of Biostructures and Bioimaging, C.N.R., Naples, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Pedone
authors.affiliation: Institute of Biostructures and Bioimaging, C.N.R., Naples, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Di Gaetano
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Capasso
authors.affiliation: Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Evan F
authors.initials: EF
authors.lastname: Haney
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Izzo
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Varcamonti
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Notomista
authors.affiliation: Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Di Donato
authors.affiliation: Department of Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Pizzo
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics*; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001057:Apolipoproteins E; D007155:Immunologic Factors; D008070:Lipopolysaccharides
keywords: antimicrobial peptides; apolipoprotein E; immunomodulation; inflammation; lipopolysaccharide