A novel antimicrobial peptide acting via formyl peptide receptor 2 shows therapeutic effects against rheumatoid arthritis

Sci Rep. 2018 Oct 2;8(1):14664. doi: 10.1038/s41598-018-32963-5.

Abstract

In oriental medicine, centipede Scolopendra subspinipes mutilans has long been used as a remedy for rheumatoid arthritis (RA), a well-known chronic autoimmune disorder. However, the molecular identities of its bioactive components have not yet been extensively investigated. We sought to identify bioactive molecules that control RA with a centipede. A novel antimicrobial peptide (AMP) (scolopendrasin IX) was identified from Scolopendra subspinipes mutilans. Scolopendrasin IX markedly activated mouse neutrophils, by enhancing cytosolic calcium increase, chemotactic cellular migration, and generation of superoxide anion in neutrophils. As a target receptor for scolopendrasin IX, formyl peptide receptor (FPR)2 mediates neutrophil activation induced by the AMP. Furthermore, scolopendrasin IX administration strongly blocked the clinical phenotype of RA in an autoantibody-injected model. Mechanistically, the novel AMP inhibited inflammatory cytokine synthesis from the joints and neutrophil recruitment into the joint area. Collectively, we suggest that scolopendrasin IX is a novel potential therapeutic agent for the control of RA via FPR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antimicrobial Cationic Peptides / therapeutic use
  • Antirheumatic Agents / chemical synthesis
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthropods
  • Autoantibodies / administration & dosage
  • Autoantibodies / blood
  • Cells, Cultured
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Humans
  • Injections, Subcutaneous
  • Insect Proteins / chemical synthesis
  • Insect Proteins / pharmacology*
  • Insect Proteins / therapeutic use
  • Male
  • Mice
  • Mice, Transgenic
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Primary Cell Culture
  • Receptors, Formyl Peptide / immunology
  • Receptors, Formyl Peptide / metabolism*
  • Treatment Outcome

Substances

  • Antimicrobial Cationic Peptides
  • Antirheumatic Agents
  • Autoantibodies
  • Insect Proteins
  • Receptors, Formyl Peptide
  • formyl peptide receptor 2, mouse