The potential role of interleukin‐17 in the immunopathology of periodontal disease

Abstract

Interleukin-17 (IL-17) is exclusively produced by activated T cells, and this cytokine can induce inflammatory responses, support immune responses (Th1), and stimulate osteoclastic bone resorption in combination with receptor activator of NF-kappaB (RANK) and RANK ligand (RANKL). These biological functions are relevant to the aetiopathogenesis of periodontitis, and thus we sought to investigate whether IL-17 is produced in periodontal lesions and to assess the relationship of gene expression between IL-17 and other cytokines, and to determine the effect of IL-17 on IL-6 production in human gingival fibroblasts (HGF). IL-17 was detected and measured in periodontal tissues obtained as biopsy samples during periodontal surgery and in the cell-free culture supernatants cultured ex vivo, by using Western immunoblotting and enzyme-linked immunosorbent assay, respectively. IL-17 and other cytokine gene expression were investigated by the reverse transcription-polymerase chain reaction (RT-PCR) method. The contribution of IL-17 to IL-6 production by HGF was studied. IL-17 protein was moderately detected in periodontal tissues. In contrast, IL-17 mRNA was expressed only in nine of 23 periodontitis tissue samples by RT-PCR. The IL-17 mRNA-positive samples simultaneously expressed mRNAs encoding interferon (IFN)-gamma, IL-2, RANK, and RANKL, but not IL-4. IL-10 (Th2 cytokine) was detected more frequently in the samples than IFN-gamma and IL-2 (Th1 cytokine). Recombinant human IL-17 induced IL-6 production from HGF in a dose- and time-dependent fashion. These results indicate that IL-17 is produced in periodontal lesions, which may be involved in Th1 modulation and enhance inflammatory reactions via gingival fibroblast-derived mediators in periodontal disease. Thus, IL-17, together with other cytokines, has a potential role in the aetiopathogenesis of periodontal disease.