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Tumor necrosis factor-alpha stimulates gingival epithelial cells to release high mobility-group box 1
Authors:Morimoto Y  Kawahara K-I  Tancharoen S  Kikuchi K  Matsuyama T  Hashiguchi T  Izumi Y  Maruyama I
Institution:Department of Periodontology;and Department of Laboratory and Vascular Medicine, Cardiovascular and Respiratory Disorders, Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan;, Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand;and Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
Abstract:Background and Objective: High‐mobility‐group box 1 functions as a late‐phase inflammatory mediator. It can be released extracellularly by macrophages and necrotic cells through lipopolysaccharide and tumor necrosis factor‐α. The objective of this study was to clarify the source of high‐mobility‐group box 1 in chronic periodontitis tissues and tumor necrosis factor‐α‐stimulated gingival epithelial cells, and subsequently elucidate its inducible inflammatory pathway. Material and Methods: Chronic periodontitis and healthy gingival sections were stained for high‐mobility‐group box 1 by immunohistochemistry and immunofluorescence. The amounts of high‐mobility‐group box 1 released into the gingival crevicular fluid and supernatants from gingival epithelial cells stimulated by tumor necrosis factor‐α were examined by western blot. The phosphorylation of mitogen‐activated protein kinases (MAPKs) in gingival epithelial cells was also examined. Results: High‐mobility‐group box 1 was detected in the cytoplasm and nucleus of gingival epithelial cells with periodontitis. Western blotting revealed a significant increase in high‐mobility‐group box 1 expression in the gingival crevicular fluid from periodontitis patients. High‐mobility‐group box 1 production in gingival epithelial cells was increased following stimulation with tumor necrosis factor‐α. The molecular dialogue between tumor necrosis factor‐α and gingival epithelial cells involved modulation of the activities of p38MAPK, Jun N‐terminal kinase and p44/42. Interestingly, only phosphorylation of p38MAPK contributed to more than half of the signaling initiated by tumor necrosis factor‐α‐elicited high‐mobility‐group box 1 release. Conclusion: High‐mobility‐group box 1 is continuously released from the gingival epithelial cells modulated by tumor necrosis factor‐α. These findings imply that high‐mobility‐group box 1 expression and possibly p38MAPK constitute important features in periodontitis.
Keywords:gingival epithelial cell  high mobility-group box 1  periodontitis  tumor necrosis factor-α
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