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

Raja Azman, David F. Lappin, Alexandrea MacPherson, Marcello Riggio, Douglas Robertson, Penny Hodge, Gordon Ramage, Shauna Culshaw, Philip M. Preshaw, John Taylor, Christopher Nile (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1001-1012
Number of pages12
JournalInflammation Research
Volume63
Issue number12
Early online date5 Nov 2014
DOIs
Publication statusPublished - 13 Nov 2014

Keywords

  • IL-17
  • IL-17A
  • IL-17E
  • IL-25
  • IL-8
  • Periodontitis

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