The antimicrobial peptide LL37 induces the migration of human pulp cells: a possible adjunct for regenerative endodontics

J Endod. 2010 Jun;36(6):1009-13. doi: 10.1016/j.joen.2010.02.028. Epub 2010 Apr 14.

Abstract

Introduction: The antimicrobial peptide LL37 has multiple functions, such as the induction of angiogenesis and migration. Pulp cell migration is a key phenomenon in the early stage of pulp-dentin complex regeneration. In this study, we examined the effect of LL37 on the migration of human pulp (HP) cells.

Methods: HP cells at the sixth passage were exposed to LL37. The migration of HP cells was assessed by a wound-healing assay. The phosphorylation of epidermal growth factor receptor (EGFR) and c-Jun N-terminal kinase (JNK) was analyzed by immunoblotting.

Results: LL37 as well as heparin binding (HB)-EGF, which is an agonist of EGFR, induced HP cell migration. LL37 increased the level of phosphorylated EGFR. An anti-EGFR antibody, an EGFR tyrosine kinase inhibitor, and a JNK inhibitor abolished the migration induced by both LL37 and HB-EGF. Furthermore, the two peptides increased the levels of phosphorylated JNK.

Conclusions: LL37 activates EGFR and JNK to induce HP cell migration, and it may contribute to enhancing the regeneration of pulp-dentin complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Anthracenes / pharmacology
  • Antimicrobial Cationic Peptides
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Cathelicidins / pharmacology*
  • Cell Movement / drug effects
  • Cells, Cultured
  • Dental Pulp / cytology
  • Dental Pulp / drug effects*
  • Endodontics
  • Enzyme Inhibitors / pharmacology
  • ErbB Receptors / agonists
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / drug effects
  • Flavonoids / pharmacology
  • Heparin / pharmacology
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • Phosphorylation
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Purinergic P2 Receptor Agonists
  • Quinazolines
  • Receptors, Cell Surface / drug effects
  • Receptors, Purinergic P2X
  • Regenerative Medicine
  • Tissue Engineering / methods
  • Tyrphostins / pharmacology

Substances

  • Anthracenes
  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Enzyme Inhibitors
  • Flavonoids
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Purinergic P2 Receptor Agonists
  • Quinazolines
  • Receptors, Cell Surface
  • Receptors, Purinergic P2X
  • Tyrphostins
  • RTKI cpd
  • pyrazolanthrone
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • Adenosine Triphosphate
  • Heparin
  • ErbB Receptors
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Protein Tyrosine Phosphatases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one