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Background and Objective: CXC chemokine 10 (CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T-helper 1 cells. In this study we examined the effects of cytokines on CXCL10 production by human gingival fibroblasts. Material and Methods: Human gingival fibroblasts were exposed to pro-inflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha), a T-helper 1 cytokine (interferon-gamma), T-helper 2 cytokines (interleukin-4, interleukin-13), T-helper 17 cytokines (interleukin-17A, interleukin-22) and regulatory T-cell cytokines (interleukin-10, transforming growth factor-beta1) for 24 h. CXCL10 production by human gingival fibroblasts was examined by enzyme-linked immunosorbent assay. Results: Human gingival fibroblasts produced CXCL10 protein upon stimulation with interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma. Treatment of human gingival fibroblasts with interferon-gamma in combination with tumor necrosis factor-alpha or interleukin-1beta resulted in a synergistic production of CXCL10. However, interleukin-4 and interleukin-13 inhibited CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated-human gingival fibroblasts. On the other hand, interleukin-17A and interleukin-22 enhanced CXCL10 production by human gingival fibroblasts treated with interferon-gamma and inhibited CXCL10 production by tumor necrosis factor-alpha-stimulated human gingival fibroblasts. Furthermore, the anti-inflammatory cytokine, interleukin-10, inhibited CXCL10 production by both interferon-gamma- and tumor necrosis factor-alpha-stimulated human gingival fibroblasts, but transforming growth factor-beta1 enhanced interferon-gamma-mediated CXCL10 production by human gingival fibroblasts. Conclusion: These results mean that the balance of cytokines in periodontally diseased tissue may be essential for the control of CXCL10 production by human gingival fibroblasts, and the production of CXCL10 might be important for the regulation of T-helper 1 cell infiltration in periodontally diseased tissue. [ABSTRACT FROM AUTHOR]

Objectives: Periodontal disease is a chronic inflammatory disease caused by periodontopathogenic bacteria, and its progression leads to periodontal tissue destruction and tooth loss. Zerumbone is a bioactive substance found in ginger ( Zingiber zerumbet ) and is known to have bioactive effects such as anticancer effects, but there have been no attempts to use it for periodontitis treatment. In addition, there have been no reports examining its effects on periodontal tissue component cells. In this experiment, we aimed to determine whether zerumbone affects the production of inflammatory mediators induced by tumor necrosis factor (TNF)-α in human periodontal ligament cells (HPDLCs), including its effects on signaling pathways., Methods: HPDLCs were stimulated by TNF-α (10 ng/ml) with or without zerumbone (6.25, 12.5, or 25 µM). Cytokine production in supernatant was determined using ELISA. Activation of signal transduction pathways and intracellular protein expression were investigated using the western blot analysis., Results: Zerumbone significantly suppressed TNF-α-induced production of CC chemokine ligand 2 (CCL2), CCL20, CXC chemokine ligand 10 (CXCL10), and interleukin-6 (IL-6) in HPDLCs. In addition, zerumbone decreased intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2) expression in TNF-α-stimulated HPDLCs. Furthermore, zerumbone suppressed activation of nuclear factor (NF)-κB and signal transducer and activator of transcription 3 (STAT3) pathways in TNF-α-treated HPDLCs. Finally, zerumbone enhanced the production of heme oxygenase-1 (HO-1), an antioxidant enzyme, in HPDLCs., Conclusion: These results suggest that zerumbone suppressed the production of several inflammatory mediators by inhibiting the NF-κB and STAT3 pathways in HPDLCs.