Biological effects of interleukin‐6 on Gingival Fibroblasts: Cytokine regulation in periodontitis

  • Koji Naruishi
    Department of Periodontology and Endodontology, Institute of Biomedical Sciences Tokushima University Graduate School Kuramoto Tokushima Japan
  • Toshihiko Nagata
    Department of Periodontology and Endodontology, Institute of Biomedical Sciences Tokushima University Graduate School Kuramoto Tokushima Japan

書誌事項

公開日
2018-03-25
資源種別
journal article
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/jcp.26521
公開者
Wiley

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説明

<jats:sec><jats:label/><jats:p>Periodontitis is a bacterial infectious disease, and many inflammatory cytokines regulate periodontitis pathophysiology through a crosstalk between tissue cells and immune cells. Interleukin (IL)‐6 is an important cytokine involved in the regulation of host response to bacterial infection. Human Gingival Fibroblasts (HGFs) are the most abundant cells in gingival connective tissues. Various HGF responses to periodontal pathogens or inflammatory cytokines contribute to the development of periodontitis. Lipopolysaccharide derived from <jats:italic>Porphyromonas gingivalis</jats:italic> (Pg LPS) and IL‐1β significantly increase IL‐6 production in HGFs. However, IL‐6 cannot function in HGFs without the soluble form of the IL‐6 receptor (sIL‐6R), because HGFs do not express sufficient cell surface IL‐6R to bind appreciable levels of IL‐6. Importantly, sIL‐6R is essential for IL‐6 signaling in HGFs, and the sIL‐6R is produced by differentiated THP‐1 cells treated with IL‐6. Calprotectin, a heterodimer of S100A8 and S100A9, is released during inflammation and significantly induces IL‐6 production in HGFs via toll‐like receptor 4 (TLR4)/nuclear factor‐kappa B (NF‐κB) signals. Calprotectin also induces sIL‐6R production in differentiated THP‐1 cells. IL‐6 induces vascular endothelial growth factor (VEGF), matrix‐metalloproteinase‐1 (MMP‐1), and cathepsin L production in HGFs in the presence of sIL‐6R. Taken together, calprotectin‐induced IL‐6 production in HGFs may cause periodontitis progression through a crosstalk of fibroblasts and macrophages. There are many reports that examine how cytokines are released from HGFs to cause beneficial or harmful effects in inflamed periodontal lesions. This review explores the pathophysiology of periodontitis by focusing IL‐6‐mediated crosstalk of HGFs and macrophages.</jats:p></jats:sec>

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