New perspectives for natural antimicrobial peptides: application as antinflammatory drugs in a murine model

BMC Immunol. 2012 Nov 17:13:61. doi: 10.1186/1471-2172-13-61.

Abstract

Background: Antimicrobial peptides (AMPs) are an ancient group of defense molecules. AMPs are widely distributed in nature (being present in mammals, birds, amphibians, insects, plants, and microorganisms). They display bactericidal as well as immunomodulatory properties. The aim of this study was to investigate the antimicrobial and anti-inflammatory activities of a combination of two AMPs (temporin B and the royal jellein I) against Staphylococcus epidermidis.

Results: The temporin B (TB-KK) and the royal jelleins I, II, III chemically modified at the C terminal (RJI-C, RJII-C, RJIII-C), were tested for their activity against 10 different Staphylococcus epidermidis strains, alone and in combination. Of the three royal jelleins, RJI-C showed the highest activity. Moreover, the combination of RJI-C and TB-KK (MIX) displayed synergistic activity. In vitro, the MIX displayed low hemolytic activity, no NO2- production and the ability to curb the synthesis of the pro-inflammatory cytokines TNF-α and IFN-γ to the same extent as acetylsalicylic acid. In vivo, the MIX sterilized mice infected with Staphylococcus epidermidis in eleven days and inhibited the expression of genes encoding the prostaglandin-endoperoxide synthase 2 (COX-2) and CD64, two important parameters of inflammation.

Conclusion: The study shows that the MIX - a combination of two naturally occurring peptides - displays both antimicrobial and anti-inflammatory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Antimicrobial Cationic Peptides / administration & dosage
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antimicrobial Cationic Peptides / therapeutic use
  • Bacterial Load / drug effects
  • Cell Death / drug effects
  • Disease Models, Animal
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Gentamicins / pharmacology
  • Hemolysis / drug effects
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Nitrates / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus epidermidis / drug effects

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Antimicrobial Cationic Peptides
  • Gentamicins
  • Lipopolysaccharides
  • Nitrates
  • RNA, Messenger