A new cryptic cationic antimicrobial peptide from human apolipoprotein E with antibacterial activity and immunomodulatory effects on human cells

Katia Pane, Valeria Sgambati, Anna Zanfardino, Giovanni Smaldone, Valeria Cafaro, Tiziana Angrisano, Emilia Pedone, Sonia Di Gaetano, Domenica Capasso, Evan F. Haney, Viviana Izzo, Mario Varcamonti, Eugenio Notomista, Robert E.W. Hancock, Alberto Di Donato, Elio Pizzo

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2115-2131
Number of pages17
JournalFEBS Journal
Issue number11
Publication statusPublished - 1 Jun 2016
Externally publishedYes


  • antimicrobial peptides
  • apolipoprotein E
  • immunomodulation
  • inflammation
  • lipopolysaccharide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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