Pocket Epithelium in the Pathological Setting for HMGB1 Release

  • N. Ebe
    Section of Periodontology
  • M. Hara-Yokoyama
    Section of Biochemistry, Department of Hard Tissue Engineering, Biochemistry, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan
  • K. Iwasaki
    Section of Periodontology
  • S. Iseki
    Department of Molecular Craniofacial Embryology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan
  • S. Okuhara
    Department of Molecular Craniofacial Embryology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan
  • K.A. Podyma-Inoue
    Section of Biochemistry, Department of Hard Tissue Engineering, Biochemistry, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan
  • K. Terasawa
    Section of Biochemistry, Department of Hard Tissue Engineering, Biochemistry, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan
  • A. Watanabe
    The Institute of Biomaterial and Bioengineering, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan
  • T. Akizuki
    Section of Periodontology
  • H. Watanabe
    Section of Periodontology
  • M. Yanagishita
    Section of Biochemistry, Department of Hard Tissue Engineering, Biochemistry, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan
  • Y. Izumi
    Section of Periodontology

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<jats:p> High-mobility group box-1 (HMGB1) protein acts as a transcription factor in the nucleus and also as a pro-inflammatory cytokine when released into extracellular fluids. The presence of higher levels of HMGB1 is reported in the gingival crevicular fluid from periodontal patients. Since the proliferation of bacteria within the periodontal pocket is closely involved in the exacerbation of periodontal disease, it is hypothesized that the periodontal pocket causes the release of HMGB1. Immunohistochemical staining of inflamed gingiva revealed that HMGB1 is exclusively dislocated from the nucleus to the cytoplasm in the pocket epithelium, whereas it is mainly present in the nucleus in the gingival epithelium. Butyric acid, an extracellular metabolite from periodontopathic bacteria populating the periodontal pocket, induced the passive release of HMGB1 as a result of eliciting necrosis in the human gingival epithelial cell line. Thus, the periodontal epithelium may provide a unique pathological setting for HMGB1 release by bacterial insult. Abbreviations: HMGB1, high-mobility group box-1; TNF-α, tumor necrosis factor-α; CHX, cycloheximide; PI, propidium iodide; ROS, reactive oxygen species; HDAC, histone deacetylase. </jats:p>

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