title: The antimicrobial peptide LL37 induces the migration of human pulp cells: a possible adjunct for regenerative endodontics.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komatsuzawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ouhara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Yuushi
authors.initials: Y
authors.lastname: Uchida
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Mizuno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D054804:Cathelicidins / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D004708:Endodontics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D058910:Purinergic P2 Receptor Agonists; D011799:Quinazolines; D011956:Receptors, Cell Surface / Q000187:drug effects; D058469:Receptors, Purinergic P2X; D044968:Regenerative Medicine; D023822:Tissue Engineering / Q000379:methods; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D004791:Enzyme Inhibitors; D005419:Flavonoids; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D058910:Purinergic P2 Receptor Agonists; D011799:Quinazolines; D011956:Receptors, Cell Surface; D058469:Receptors, Purinergic P2X; D020032:Tyrphostins; C101044:RTKI cpd; C432165:pyrazolanthrone; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D006493:Heparin; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one