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FEBS J. 2016 Jun;283(11):2115-31. doi: 10.1111/febs.13725. Epub 2016 Apr 20.

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

Author information

1
Department of Biology, University of Naples Federico II, Naples, Italy.
2
Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
3
IRCCS SDN, Naples, Italy.
4
Institute of Biostructures and Bioimaging, C.N.R., Naples, Italy.
5
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
6
Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.

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.

KEYWORDS:

antimicrobial peptides; apolipoprotein E; immunomodulation; inflammation; lipopolysaccharide

PMID:
27028511
DOI:
10.1111/febs.13725
[Indexed for MEDLINE]
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