IL-17-Family Cytokines and Periodontitis: Differential Roles for IL-17A and IL-17E?

Objectives: While IL-17A is implicated in periodontitis pathogenesis, the roles of the other family members IL-17B - IL-17F and IL-17A/F are less well defined. 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.
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 and mRNA from healthy and periodontitis tissue biopsy samples by reverse transcription PCR. Oral keratinocytes (which do not synthesise IL-17A or IL-17E, but express their receptors) were stimulated with a P. gingivalis biofilm, or with recombinant IL-17A, in the presence and absence of recombinant IL-17E and the expression of CXCL5and CXCL8 (IL-8) were investigated by ELISA and real-time-PCR. In similar experiments, NF-κB p65 subunit phosphorylation was also measured using a cell-based ELISA.
Results: Serum, saliva and GCF IL-17A and IL-17A mRNA levels were higher in periodontitis patients and correlated positively with clinical parameters of attachment loss (AL), pocket depth (PD) and bleeding on probing (BOP). Serum IL-17E levels were lower, but GCF levels of IL-17E were greater in periodontitis patients; in-line with higher IL-17E mRNA levels in periodontitis tissue samples. Nevertheless, GCF IL-17A:IL-17E correlated positively with PD, while serum IL-17A:IL-17E correlated positively with AL, PD & BOP. In vitro, IL-17E inhibited P. gingivalis and IL-17A induced expression of CXCL5 & CXCL8 and reduced 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 P. gingivalis induced expression of chemokines.