Human gingival fibroblasts release high-mobility group box-1 protein through active and passive pathways
Human gingival fibroblasts release high-mobility group box-1 protein through active and passive pathways
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DOI：
10.1111/j.1399-302x.2009.00508.x
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发表时间：
2009-08-01
影响因子：
--
通讯作者：
Izumi, Y.
中科院分区：
文献类型：
--
作者：
Feghali, K.;Iwasaki, K.;Izumi, Y.
简介：核蛋白高迁移率族蛋白1（HMGB1）在细胞外环境中分泌时作为炎症的晚期介质。在这项研究中，我们研究了从牙周病原体和凋亡和坏死细胞死亡的脂多糖对HMGB1的生产在人牙龈成纤维细胞（HGF）的影响。方法：从健康牙周组织培养HGF和刺激的脂多糖（LPS）从伴放线菌聚集菌，牙龈卟啉单胞菌，大肠杆菌。我们还在HGF中启动了凋亡和坏死细胞死亡。测定刺激或死亡细胞上清液中释放的HMGB1。结果：HMGB1在坏死和凋亡的肝细胞生长因子中的表达量明显增加。LPS来自A.放线菌共生菌、牙龈卟啉单胞菌和E.大肠杆菌诱导HMGB1的产生具有时间依赖性。LPS刺激6h后，HMGB1主要定位于细胞质，24h后主要定位于细胞核。放线菌共生菌和牙龈卟啉单胞菌诱导HGF分泌HMGB1。凋亡和坏死细胞死亡导致HMGB1的增强。我们的研究结果表明，肝细胞生长因子可以通过主动分泌和被动释放的HMGB1的来源，从肝细胞生长因子HMGB1可能有助于牙周组织的破坏。
Introduction: The nuclear protein high-mobility group box-1 (HMGB1) acts as a late mediator of inflammation when secreted in the extracellular milieu. In this study, we examined the effect of lipopolysaccharides from periodontal pathogens and apoptotic and necrotic cell death on HMGB1 production in human gingival fibroblasts (HGF).Methods: HGF from healthy periodontal tissue were cultured and stimulated with lipopolysaccharides (LPS) from Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Escherichia coli. We also initiated apoptotic and necrotic cell deaths in HGF. The HMGB1 released in the supernatants from stimulated or dying cells was measured. Immunocytochemical staining against HMGB1 was performed in LPS-stimulated HGF.Results: A significantly higher amount of HMGB1 was detected from necrotic and apoptotic HGF. LPS from A. actinomycetemcomitans, P. gingivalis, and E. coli significantly induced the production of HMGB1 in a time-dependent manner. After 6 h of LPS stimulation, HMGB1 was present in the cytoplasm of cells whereas its location was mainly nuclear after 24 h.Conclusions: LPS from two major periodontal pathogens, A. actinomycetemcomitans and P. gingivalis, induced HMGB1 secretion from HGF. Apoptotic and necrotic cell deaths resulted in the enhancement of HMGB1. Our results suggest that HGF can be a source of HMGB1 by both active secretion and passive release, and that HMGB1 from HGF may contribute to periodontal tissue destruction.