Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease
Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease
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DOI：
10.1111/j.1600-0765.2007.01041.x
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发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Wang, Pao-Li
中科院分区：
文献类型：
--
作者：
Ara, Toshiaki;Kurata, Kazuyuki;Wang, Pao-Li
牙周病是一种生物被膜感染性疾病，因其能引起炎症和促进组织破坏而被认为是其发病机制中的一个主要因素。此外，消除病原体及其组成的LPS对于牙周病的成功治疗是至关重要的。内毒素耐受是防止单核细胞和巨噬细胞对内毒素过度和长期反应的一种机制。由于炎症的持续存在对于炎症细胞因子的产生是必要的，因此单核细胞和巨噬细胞以外的细胞被认为在内毒素存在的情况下维持细胞因子的产生。本研究旨在探讨牙周组织中含量最丰富的结构细胞--牙周成纤维细胞(HGFs)能否通过不表现出对LPS的耐受性来维持炎症细胞因子的产生。此外，我们还检测了细胞因子信号转导抑制因子-1、白介素1受体相关激酶M和含SH2结构域的肌醇-5-磷酸酶-1等负性信号调节因子在HGFs中的表达。脂多糖处理的HGFs不表达负调控因子，这些结果表明HGFs不表现出对内毒素的耐受，提示HGFs的这一特性支持在毒力因子存在的情况下的炎症反应。
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.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.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.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.