Clinical associations between IL-17 family cytokines and periodontitis and potential differential roles for IL-17A and IL-17E in periodontal immunity

Inflamm Res. 2014 Dec;63(12):1001-12. doi: 10.1007/s00011-014-0776-7. Epub 2014 Nov 5.

Abstract

Objective: IL-17A is implicated in periodontitis pathogenesis. The roles of IL-17B-IL-17F and IL-17A/F are unknown. This study aimed to determine clinical associations between IL-17 family cytokines and periodontitis and to investigate the biological roles of IL-17A and IL-17E using in vitro model systems.

Materials and methods: Samples from 97 patients with periodontitis and 77 healthy volunteers were used in the study. Serum, saliva and gingival crevicular fluid (GCF) levels of IL-17 family cytokines were measured by ELISA. Oral keratinocytes were stimulated with a P. gingivalis biofilm, or IL-17A, in the presence and absence of IL-17E and the expression of IL-8 and CXCL5 were investigated by ELISA and real-time-PCR. NF-κB phosphorylation in similar experiments was also measured using a cell-based ELISA.

Results: Serum, saliva and GCF IL-17A levels were higher in periodontitis patients and correlated positively with clinical parameters of attachment loss, pocket depth and bleeding on probing. Serum IL-17E levels were lower in periodontitis patients and the serum IL-17A:IL-17E ratio correlated positively with clinical parameters. In vitro, IL-17E inhibited Porphyromonas gingivalis and IL-17A induced expression of chemokines by reducing phosphorylation of the NF-κB p65 subunit.

Conclusions: Serum IL-17A:IL-17E may be a marker of disease severity. IL-17E may have opposing roles to IL-17A in periodontitis pathogenesis. IL-17E can negatively regulate IL-17A and periodontal pathogen induced expression of chemokines by oral keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biofilms
  • Biomarkers / blood
  • Case-Control Studies
  • Coculture Techniques
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation*
  • Gingival Crevicular Fluid / immunology
  • Humans
  • Interleukin-17 / metabolism*
  • Keratinocytes / cytology
  • Male
  • Middle Aged
  • Periodontitis / immunology*
  • Periodontitis / metabolism*
  • Porphyromonas gingivalis / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-17