The expression and regulation of matrix metalloproteinase-3 is critically modulated by Porphyromonas gingivalis lipopolysaccharide with heterogeneous lipid A structures in human gingival fibroblasts.
The expression and regulation of matrix metalloproteinase-3 is critically modulated by Porphyromonas gingivalis lipopolysaccharide with heterogeneous lipid A structures in human gingival fibroblasts.
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DOI：
10.1186/1471-2180-13-73
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发表时间：
2013-03-30
期刊：
影响因子：
4.2
通讯作者：
Jin L
中科院分区：
文献类型：
--
作者：
Herath TD;Wang Y;Seneviratne CJ;Darveau RP;Wang CY;Jin L
牙龈卟啉单胞菌脂多糖（Porphyromonasgingivalis lipopolysaccharide，LPS）是一种与慢性牙周炎密切相关的重要毒力因子。它表现出显著的异质性，含有四-（LPS 1435/1449）和五-（LPS 1690）酰化脂质A结构。人牙龈成纤维细胞（HGFs）作为牙龈的主要驻留细胞，在调节基质金属蛋白酶（MMPs）和维持牙周环境稳定方面发挥着重要作用。本研究探讨牙龈卟啉单胞菌LPS 1435/1449和LPS 1690及六酰化E. coli LPS作为参照。采用实时荧光定量PCR和ELISA检测MMP 1-3和TIMP-1的表达。牙龈卟啉单胞菌LPS 1690和E. coli LPS处理的细胞中，而在牙龈卟啉单胞菌LPS 1435/1449处理的细胞中没有观察到诱导。相反，牙龈卟啉单胞菌LPS脂质A异质性对MMP-1和MMP-2的表达没有显著影响。TIMP-1 mRNA在牙龈卟啉单胞菌LPS 1435/1449-和E. coli LPS处理的细胞。接下来，通过阻断试验检查参与牙龈卟啉单胞菌LPS诱导的MMP-3表达的信号转导途径。阻断p38 MAPK和ERK可显著抑制牙龈卟啉单胞菌LPS 1690诱导的HGF中MMP-3的表达。提示牙龈卟啉单胞菌脂多糖的脂质A结构对牙龈成纤维细胞中MMP-3的表达具有不同的调节作用，可能在牙周病的发病机制中发挥作用。
Porphyromonas gingivalis lipopolysaccharide (LPS) is a crucial virulence factor strongly associated with chronic periodontitis which is the primary cause of tooth loss in adults. It exhibits remarkable heterogeneity containing tetra-(LPS1435/1449) and penta-(LPS1690) acylated lipid A structures. Human gingival fibroblasts (HGFs) as the main resident cells of human gingiva play a key role in regulating matrix metalloproteinases (MMPs) and contribute to periodontal homeostasis. This study investigated the expression and regulation of MMPs1-3 and tissue inhibitors of MMP-1 (TIMP-1) in HGFs in response to P. gingivalis LPS1435/1449 and LPS1690 and hexa-acylated E. coli LPS as a reference. The expression of MMPs 1–3 and TIMP-1 was evaluated by real-time PCR and ELISA. The MMP-3 mRNA and protein were highly upregulated in P. gingivalis LPS1690- and E. coli LPS-treated cells, whereas no induction was observed in P. gingivalis LPS1435/1449-treated cells. On the contrary, the expression of MMP-1 and −2 was not significantly affected by P. gingivalis LPS lipid A heterogeneity. The TIMP-1 mRNA was upregulated in P. gingivalis LPS1435/1449- and E. coli LPS-treated cells. Next, signal transduction pathways involved in P. gingivalis LPS-induced expression of MMP-3 were examined by blocking assays. Blockage of p38 MAPK and ERK significantly inhibited P. gingivalis LPS1690-induced MMP-3 expression in HGFs. The present findings suggest that the heterogeneous lipid A structures of P. gingivalis LPS differentially modulate the expression of MMP-3 in HGFs, which may play a role in periodontal pathogenesis.
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DOI：
10.1152/ajpheart.00928.2007
发表时间：
2007-12-01
影响因子：
4.8
作者：
Cortez, Dolores M.;Feldman, Marc D.;Chandrasekar, Bysani
通讯作者：
Chandrasekar, Bysani
Keystone-Pathogen假设。
DOI：
10.1038/nrmicro2873
发表时间：
2012-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1006/bbrc.1999.1551
发表时间：
1999-10-22
影响因子：
3.1
作者：
Bond, M;Baker, AH;Newby, AC
通讯作者：
Newby, AC
影响因子：
1.9
作者：
Domeij, H;Yucel-Lindberg, T;Modéer, T
通讯作者：
Modéer, T
影响因子：
5.6
作者：
Andrian, E;Grenier, D;Rouabhia, M
通讯作者：
Rouabhia, M