Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease |
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Authors: | Toshiaki Ara Kazuyuki Kurata Kaname Hirai Takayuki Uchihashi Takashi Uematsu Yasuhiro Imamura Kiyohumi Furusawa Saburo Kurihara Pao-Li Wang |
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Affiliation: | Departments of Pharmacology;, Orthodontics;, Oral Microbiology;and Oral and Maxillofacial Surgery, Matsumoto Dental University, 1780 Gobara, Hirooka, Shiojiri, Nagano 399-0781, Japan |
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Abstract: | Background and Objective: A major factor in the pathogenesis of periodontal disease, which is one of the biofilm infectious diseases, is thought to be lipopolysaccharide (LPS), owing to its ability to cause inflammation and promote tissue destruction. Moreover, the elimination of pathogens and their component LPSs is essential for the successful treatment of periodontal disease. Lipopolysaccharide tolerance is a mechanism that prevents excessive and prolonged responses of monocytes and macrophages to LPS. Since persistence of inflammation is necessary for inflammatory cytokine production, cells other than monocytes and macrophages are thought to maintain the production of cytokines in the presence of LPS. In this study, we investigated whether human gingival fibroblasts (HGFs), the most abundant structural cell in periodontal tissue, might be able to maintain inflammatory cytokine production in the presence of LPS by not displaying LPS tolerance. Material and Methods: Human gingival fibroblasts were pretreated with LPS (from Porphyromonas gingivalis and Escherichia coli ) and then treated with LPS, and the amounts of interleukin (IL)-6 and IL-8 in the cell culture supernatants were measured. The expression of negative regulators of LPS signalling (suppressor of cytokine signalling-1, interleukin-1 receptor-associated-kinase M and SH2 domain-containing inositol-5-phosphatase-1) was also examined in LPS-treated HGFs. Results: Human gingival fibroblasts did not display LPS tolerance but maintained production of IL-6 and IL-8 when pretreated with LPS, followed by secondary LPS treatment. Lipopolysaccharide-treated HGFs did not express negative regulators. Conclusion: These results demonstrate that HGFs do not show LPS tolerance and suggest that this characteristic of HGFs sustains the inflammatory response in the presence of virulence factors. |
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Keywords: | human gingival fibroblast inflammatory cytokine lipopolysaccharide tolerance peripheral blood mononuclear cell |
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