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A new cryptic cationic antimicrobial peptide from human apolipoprotein E with antibacterial activity and immunomodulatory effects on human cells
Author(s) -
Pane Katia,
Sgambati Valeria,
Zanfardino Anna,
Smaldone Giovanni,
Cafaro Valeria,
Angrisano Tiziana,
Pedone Emilia,
Di Gaetano Sonia,
Capasso Domenica,
Haney Evan F.,
Izzo Viviana,
Varcamonti Mario,
Notomista Eugenio,
Hancock Robert E.W.,
Di Donato Alberto,
Pizzo Elio
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13725
Subject(s) - antimicrobial peptides , chemokine , lipopolysaccharide , proinflammatory cytokine , innate immune system , recombinant dna , antimicrobial , lipid a , beta defensin , escherichia coli , peptide , biology , microbiology and biotechnology , immune system , inflammation , chemistry , biochemistry , immunology , gene
Cationic antimicrobial peptides ( AMP s) 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 AMP s, 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 AMP s, 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 PBMC s. 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.