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

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. 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-kappa B phosphorylation in similar experiments was also measured using a cell-based ELISA. 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-kappa B p65 subunit. 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.