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Background/Aims: Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of various diseases in traditional oriental medicine. Genipin has been used as a blue colorant in food industry. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify CCL20 and IL-6, which are related to bone resorption in periodontal disease, expression in human periodontal ligament cells (HPDLCs). Methods: CCL20 and IL-6 productions from HPDLCs were determined by ELISA. Western blot analysis was used for the detection of signal transduction molecules expressions in HPDLCs. Results: Genipin prevented IL-1β-mediated CCL20 and IL-6 production in HPDLCs. Moreover, genipin could suppress nuclear factor kappa B (NF-κB) p65, extracellular signalregulated kinase (ERK) and MAPK/ERK kinase (MEK) phosphorylations in IL-1β-stimulated HPDLCs. NF-κB inhibitor and ERK inhibitor significantly inhibited IL-6 and CCL20 productions from IL-1β-stimulated HPDLCs. Conclusions: These data provide a novel mechanism through which genipin could be used to provide direct benefits in periodontal disease to inhibit IL-6 and CCL20 productions in periodontal lesions. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Highlights: [•] TLR3 ligand induced CCL20 production from human gingival fibroblasts (HGFs). [•] TLR3 ligand synergistically enhanced CCL20 production from IL-1β-stimulated HGFs. [•] p38 MAPK, JNK and NF-κB activations are related with CCL20 production in HGFs. [ABSTRACT FROM AUTHOR]

Abstract: CC chemokine ligand 20 (CCL20) is related to T-helper (Th)-17 cell migration, and Th17 cells play important roles in exacerbation in periodontal disease. However, the effect of tumor necrosis factor–like weak inducer of apoptosis (TWEAK) on CCL20 production is unknown. In this study, we examined the mechanisms of TWEAK in combination with interleukin (IL)-1β-induced CCL20 production in human gingival fibroblasts (HGFs). TWEAK alone did not induce CCL20 production in HGFs. However, TWEAK enhanced CCL20 expression from IL-1β-stimulated HGFs in a dose-dependent manner. Inhibitors of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and nuclear factor κB (NF-κB) significantly inhibited CCL20 production in TWEAK and IL-1β-stimulated HGFs. Western blot analysis revealed that phosphorylations of ERK, Akt, and inhibitor of NF-κB were enhanced in TWEAK and IL-1β-treated HGFs. These data suggest that TWEAK is positively related to Th17 cell migration in periodontally diseased tissues to enhance CCL20 production in IL-1β-stimulated HGFs. [Copyright &y& Elsevier]