LL-37 in periodontal health and disease and its susceptibility to degradation by proteinases present in gingival crevicular fluid

• Published in: Journal of clinical periodontology Vol. 40; no. 10; pp. 933 - 941
• Main Authors: McCrudden, Maelíosa T. C., Orr, David F., Yu, Yang, Coulter, Wilson A., Manning, Gwen, Irwin, Chris R., Lundy, Fionnuala T.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.10.2013
• Subjects: Adhesins, Bacterial - analysis; Adhesins, Bacterial - drug effects; Adult; Aged; Anti-Bacterial Agents - analysis; Antimicrobial Cationic Peptides; antimicrobial peptide; cathelicidin; Cathelicidins - analysis; Cysteine Endopeptidases - analysis; Cysteine Endopeptidases - drug effects; Cysteine Proteases - metabolism; Cysteine Proteinase Inhibitors - pharmacology; Dental Plaque - microbiology; Dentistry; Desorption; Enzyme-Linked Immunosorbent Assay; Gingipain Cysteine Endopeptidases; Gingival Crevicular Fluid - enzymology; Gingival Crevicular Fluid - microbiology; Gum disease; Humans; Lasers; Leupeptins - pharmacology; mass spectrometry; Medical research; Middle Aged; Oral hygiene; Peptide Fragments - analysis; periodontitis; Periodontitis - enzymology; Periodontitis - metabolism; Periodontitis - microbiology; Periodontium - enzymology; Periodontium - metabolism; Porphyromonas gingivalis - enzymology; Porphyromonas gingivalis - isolation & purification; protease; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Tosyllysine Chloromethyl Ketone - pharmacology; protease; mass spectrometry; cathelicidin; antimicrobial peptide; periodontitis
• ISSN: 0303-6979; 1600-051X
• DOI: 10.1111/jcpe.12141

Aim 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. Materials and 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.