Y. MorimotoK. I. KawaharaS. TancharoenK. KikuchiT. MatsuyamaT. HashiguchiY. IzumiI. MaruyamaKagoshima University Faculty of MedicineMahidol UniversityTokyo Medical and Dental University2018-07-122018-07-122008-02-01Journal of Periodontal Research. Vol.43, No.1 (2008), 76-83002234842-s2.0-38349185374https://repository.li.mahidol.ac.th/handle/20.500.14594/19166Background 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-. The objective of this study was to clarify the source of high-mobility-group box 1 in chronic periodontitis tissues and tumor necrosis factor - 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- 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-. The molecular dialogue between tumor necrosis factor- and gingival epithelial cells involved modulation of the activities of p38MAPK, Jun N-terminal kinase and p4442. Interestingly, only phosphorylation of p38MAPK contributed to more than half of the signaling initiated by tumor necrosis factor - 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-. These findings imply that high-mobility-group box 1 expression and possibly p38MAPK constitute important features in periodontitis. © 2007 Blackwell Munksgaard.Mahidol UniversityDentistryArticleSCOPUS10.1111/j.1600-0765.2007.00996.x