title: LL-37 in periodontal health and disease and its susceptibility to degradation by proteinases present in gingival crevicular fluid.
abstract: OBJECTIVE
  To determine the levels of LL-37 in and its susceptibility to degradation by components of gingival crevicular fluid (GCF) in periodontal health and disease.
  
  
  METHODS
  Levels of LL-37 in GCF from periodontitis patients and periodontally healthy subjects were determined by ELISA. In addition, degradation of synthetic/exogenous LL-37 by components of GCF in the presence and absence of inhibitors was determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry.
  
  
  RESULTS
  The concentration of native LL-37 in GCF from Porphyromonas gingivalis positive (Pg+) and P. gingivalis negative (Pg-) sites in periodontitis patients was significantly higher than in GCF from healthy subjects. When synthetic LL-37 was added to healthy GCF, the peptide was not degraded. Conversely, GCF from Pg+ sites rapidly degraded synthetic LL-37 which was prevented in the presence of Arg- and Lys- gingipain inhibitors. Synthetic LL-37 was degraded more slowly by GCF from Pg- sites.
  
  
  CONCLUSIONS
  LL-37 is detectable in GCF in periodontal health and disease. The rapid degradation of synthetic LL-37 in periodontitis GCF, particularly in Pg+ sites, limits its role as a potential therapeutic in the gingival crevice. These results highlight the need to design stable peptide mimetics of LL-37 as future therapeutics in periodontitis.
authors: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors: Maelíosa T C
authors: MT
authors: McCrudden
authors: David F
authors: DF
authors: Orr
authors: Yang
authors: Y
authors: Yu
authors: Wilson A
authors: WA
authors: Coulter
authors: Gwen
authors: G
authors: Manning
authors: Chris R
authors: CR
authors: Irwin
authors: Fionnuala T
authors: FT
authors: Lundy
mesh_terms: D018829:Adhesins, Bacterial / Q000032:analysis / Q000187:drug effects; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000032:analysis*; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000032:analysis*; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000187:drug effects; D057056:Cysteine Proteases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003773:Dental Plaque / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D000080867:Gingipain Cysteine Endopeptidases; D005883:Gingival Crevicular Fluid / Q000201:enzymology* / Q000382:microbiology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010518:Periodontitis / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D010519:Periodontium / Q000201:enzymology / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000302:isolation & purification; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D015853:Cysteine Proteinase Inhibitors; D000080867:Gingipain Cysteine Endopeptidases; D007976:Leupeptins; D010446:Peptide Fragments; D014107:Tosyllysine Chloromethyl Ketone; D057056:Cysteine Proteases; D003546:Cysteine Endopeptidases; C032854:leupeptin
keywords: antimicrobial peptide; cathelicidin; mass spectrometry; periodontitis; protease