Porphyromonas gingivalis lipopolysaccharide induces shedding of syndecan-1 expressed by gingival epithelial cells
Porphyromonas gingivalis lipopolysaccharide induces shedding of syndecan-1 expressed by gingival epithelial cells
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DOI：
10.1002/jcp.20287
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发表时间：
2005-07-01
影响因子：
5.6
通讯作者：
Rouabhia, M
中科院分区：
文献类型：
--
作者：
Andrian, E;Grenier, D;Rouabhia, M
多配体聚糖作为正常细胞表面更新的一部分从生长的上皮细胞组成性脱落。然而，已报道在细菌感染期间发生可溶性多配体蛋白聚糖胞外域的血清水平增加。本研究的目的是评估牙周病原体牙龈卟啉单胞菌的脂多糖（LPS）诱导人牙龈上皮细胞表达的syndecan-1脱落的潜力。我们发现，syndecan-1胞外域是组成性脱落的人牙龈上皮细胞的细胞表面。当用牙龈卟啉单胞菌LPS刺激细胞时，对应于可溶性多配体蛋白聚糖-1胞外域的基础水平的这种组成性脱落显著增加，并且达到与由佛波醇肉豆蔻酸（PMA）引起的水平相当的水平，佛波醇肉豆蔻酸是蛋白激酶C（PKC）的活化剂，其众所周知是脱落激动剂。多配体蛋白聚糖-1的脱落被促炎细胞因子白细胞介素-1 β（IL-1 β）、IL-6、IL-8和肿瘤坏死因子α（TNF-α）释放所抑制。事实上，分别在牙龈卟啉单胞菌LPS和PMA刺激后，IL-1 β和TNF-α的分泌增加。当这些蛋白质的重组形式被添加到细胞培养物中时，它们诱导多配体蛋白聚糖-1胞外域脱落的浓度依赖性增加。用IL-1 β转化酶（ICE）特异性抑制剂处理阻止由牙龈卟啉单胞菌LPS刺激的上皮细胞分泌IL-1 β，并降低脱落的多配体蛋白聚糖-1胞外域的水平。我们还观察到PMA和TNF-α刺激基质金属蛋白酶-9分泌，而IL-1 β和牙龈卟啉单胞菌LPS则不刺激。我们的研究结果表明，牙龈卟啉单胞菌LPS刺激syndecan-1脱落，这种现象可能部分由IL-1 β介导，导致不同于PMA刺激的细胞内信号通路的激活。
Syndecans are constitutively shed from growing epithelial cells as the part of normal cell surface turnover. However, increased serum levels of the soluble syndecan ectodomain have been reported to occur during bacterial infections. The aim of this study was to evaluate the potential of lipopolysaccharide (LPS) from the periodontopathogen Porphyromonas gingivalis to induce the shedding of syndecan-1 expressed by human gingival epithelial cells. We showed that the syndecan-1 ectodomain is constitutively shed from the cell surface of human gingival epithelial cells. This constitutive shedding corresponding to the basal level of soluble syndecan-1 ectodomain was significantly increased when cells were stimulated with P. gingivalis LPS and reached a level comparable to that caused by phorbol myristic acid (PMA), an activator of protein kinase C (PKC) which is well known as a shedding agonist. The syndecan-1 shedding was paralleled by pro-inflammatory cytokine interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) release. Indeed, secretion of IL-1 beta and TNF-alpha increased following stimulation by P. gingivalis LPS and PMA, respectively. When recombinant forms of these proteins were added to the cell culture, they induced a concentration-dependent increase in syndecan-1 ectodomain shedding. A treatment with IL-1 beta converting enzyme (ICE) specific inhibitor prevented IL-1 beta secretion by epithelial cells stimulated by P. gingivalis LPS and decreased the levels of shed syndecan-1 ectodomain. We also observed that PMA and TNF-alpha stimulated matrix metalloproteinase-9 secretion, whereas IL-1 beta and P. gingivalis LPS did not. Our results demonstrated that P. gingivalis LPS stimulated syndecan-1 shedding, a phenomenon that may be mediated in part by IL-1 beta, leading to an activation of intracellular signaling pathways different from those involved in PMA stimulation.