Cell Penetrating Peptide Derived from Human Eosinophil Cationic Protein Decreases Airway Allergic Inflammation

Sci Rep. 2017 Sep 27;7(1):12352. doi: 10.1038/s41598-017-12390-8.

Abstract

Cell penetrating peptide derived from human eosinophil cationic protein (CPPecp) is a 10-amino-acid peptide containing a core heparan sulfate (HS)-binding motif of human eosinophil cationic protein (ECP). It binds and penetrates bronchial epithelial cells without cytotoxic effects. Here we investigated airway-protective effects of CPPecp in BEAS-2B cell line and mite-induced airway allergic inflammation in BALB/c mice. In BEAS-2B cell, CPPecp decreases ECP-induced eotaxin mRNA expression. CPPecp also decreases eotaxin secretion and p-STAT6 activation induced by ECP, as well as by IL-4. In vivo studies showed CPPecp decreased mite-induced airway inflammation in terms of eosinophil and neutrophil count in broncho-alveolar lavage fluid, peri-bronchiolar and alveolar pathology scores, cytokine production in lung protein extract including interleukin (IL)-5, IL-13, IL-17A/F, eotaxin; and pause enhancement from methacholine stimulation. CPPecp treated groups also showed lower serum mite-specific IgE level. In this study, we have demonstrated the in vitro and in vivo anti-asthma effects of CPPecp.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Asthmatic Agents / therapeutic use
  • Antigens, Dermatophagoides / immunology
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / pathology
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / immunology
  • Cell Line
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / pharmacology*
  • Cell-Penetrating Peptides / therapeutic use
  • Cytokines / immunology
  • Cytokines / metabolism
  • Drug Evaluation, Preclinical
  • Eosinophil Cationic Protein / chemistry*
  • Eosinophils / immunology
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / immunology
  • Treatment Outcome

Substances

  • Allergens
  • Anti-Asthmatic Agents
  • Antigens, Dermatophagoides
  • Cell-Penetrating Peptides
  • Cytokines
  • Recombinant Proteins
  • Eosinophil Cationic Protein
  • RNASE3 protein, human