title: The antimicrobial peptide LL-37 is anti-inflammatory and proapoptotic in human periodontal ligament cells.
abstract: OBJECTIVE
  The antimicrobial peptide LL-37 is expressed in periodontal tissue, and variations in LL-37 levels have been associated with periodontal disease. The effects of LL-37 on periodontal ligament cell function have not been described before. Here, we assess anti-inflammatory properties of LL-37 and investigate the effects of LL-37 on cell differentiation, cell proliferation and apoptosis in human periodontal ligament cells.
  
  
  METHODS
  Periodontal ligament cells were obtained from teeth extracted for orthodontic reasons. Cytokine (interleukin-6) and chemokine (monocyte chemoattractant protein-1) expression was determined by quantitative PCR, cell differentiation by alkaline phosphatase activity, cell proliferation by counting cells in a Bürker chamber, DNA synthesis by incorporation of radiolabeled thymidine and apoptosis by cell morphology and activated caspase 3 quantities.
  
  
  RESULTS
  Treatment with 0.1 and 1 μm of LL-37 totally reversed lipopolysaccharide-induced monocyte chemoattractant protein-1 expression and suppressed lipopolysaccharide-induced interleukin-6 expression by 50-70%. LL-37 had no effect on alkaline phosphatase activity. Incubation with 8 μm LL-37 strongly reduced cell number. DNA synthesis was attenuated by about 90% in response to 8 μm LL-37, confirming its antiproliferative effect. Cell morphology was altered in an apoptosis-like fashion in cells treated with 8 μm LL-37. Furthermore, the quantity of activated caspase 3 was increased in cells treated with 1 and 8 μm of LL-37, suggesting apoptosis.
  
  
  CONCLUSIONS
  LL-37 strongly attenuates lipopolysaccharide-induced cytokine and chemokine expression and, in high concentrations, reduces cell proliferation through inhibition of DNA synthesis and by promoting apoptosis in human periodontal ligament cells.
authors: Department of Periodontology, Faculty of Odontology, Malmö University, Malmö, Sweden. daniel.jonsson@mah.se
authors: D
authors: D
authors: Jönsson
authors: B-O
authors: BO
authors: Nilsson
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis / Q000187:drug effects; D002452:Cell Count; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004926:Escherichia coli; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D005810:Multigene Family; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D013936:Thymidine; D054804:Cathelicidins; D000093242:Interleukin-6 Inhibitors
chemical_list: D000469:Alkaline Phosphatase; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D053148:Caspase 3; D018932:Chemokine CCL2; D004247:DNA; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013936:Thymidine; D054804:Cathelicidins; D000093242:Interleukin-6 Inhibitors; C111835:CCL2 protein, human; C505407:CASP3 protein, human