The Effect of Genipin on Dendritic Cells Activation

Objectives: Periodontal disease is a chronic inflammation of the tooth-supporting structure due to infection by microbes in dental plaque. T helper 17(Th17) cells play a critical role in the pathogenesis of periodontal disease. Dendritic cells　(DCs) are professional antigen-presenting cells and induce Th17 cells differentiation through the secretion of Th17 cells-polarizing cytokines such as IL-6 and IL-23. Genipin, the aglycon of geniposide found in gardenia fruit, has recently been reported to have some pharmacological functions, such as anti-inflammatory effect. The aim of this study is to clarify the effect of genipin on DCs maturation and Th17 cells-polarizing cytokines expression in DCs.
Methods: To generate immature DCs, monocytes were isolated from peripheral blood mononuclear cells were cultured with GM-CSF and IL-4. After 6 days, immature DCs were stimulated with Lipid A with or without genipin pretreatment. For analysis of DCs activation, expression of MHC class 2-encoded molecule HLA-DR and co-stimulatory molecules such as CD80 and CD 86, and CD83, a specific marker of DC maturation, were analyzed by flow cytometry. We confirmed IL-6 and IL-23 productions by ELISA. To examine the activation of NF-κB, western blot analysis was performed.
Results: We elucidated genipin suppressed the Lipid A-induced expression of HLA-DR, CD80, CD86, and CD83. Moreover, genipin reduced IL-6 and IL-23 productions from Lipid A-stimulated DCs. Furthermore, genipin inhibited the degradation of IκB-α and translocation of NF-κB p65/p50 in nuclear in Lipid A-stimulated DCs.
Conclusions: These findings suggested that genipin could suppress DCs activation and Th17 cells　differentiation to inhibit IL-6 and IL-23 productions in DCs. Therefore, we might use genipin for treatment of periodontal disease because genipin could suppress bone destruction through inhibition of DCs activation and Th17 cells differentiation in periodontal lesion. This work was supported by Grant-in-Aid for Scientific Research (C) (25463219) from Japan Society for the Promotion of Science.