Abstract:
Periodontitis is a bacterial infection characterized by chronic gingival inflammation, which leads to the loss of tooth-supporting tissues. Dense infiltration of activated memory T cells and high levels of their cytokines were consistently detected in periodontal lesions. Although T cells have been considered to be central to both progression and control of chronic inflammatory periodontal diseases, the definite contribution in local immunoregulation has not been fully clarified. Recent observations showed the presence of IL-17, a novel T cell cytokine, and IFN-gamma in the inflamed periodontal tissues. Therefore, in this present study we investigated the immunostimulatory role of IL-17 and IFN-gamma on human gingival fibroblasts (HGF) which were obtained from clinically healthy periodontal tissues. Various concentrations of IL-17, IFN-gamma, or the combination of these two cytokines were added to HGF cultures. The expression of CD40 and HLA-DR was assessed by flow cytometry and IL-8 production was determined by ELISA. Our results demonstrated that IFN-gamma markedly up-regulated HLA-DR and minimally up-regulated CD40 expression on HGF. IL-17 did not induce the expression of both molecules and did not enhance IFN-gamma-induced CD40 and HLA-DR expression on HGF. Unlike IFN-gamma, IL-17 induced IL-8 production from HGF. When combined, IFN-gamma synergistically enhanced IL-17-induced IL-8 production. This enhancement was detected in all HGF cell lines at a higher dose of IL-17 (500 ng/ml) whereas at lower doses (5 and 50 ng/ml), heterogeneous response was observed. The findings of heterogeneity in IL-8 production by HGF in response to the combination of IL-17 and IFN-gamma are interesting and may explain the variation in host response in disease susceptibility or disease progression in periodontitis. Clearly, further investigation into this issue is needed.
