Loss of claudin-1 in lipopolysaccharide-treated periodontal epithelium
Loss of claudin-1 in lipopolysaccharide-treated periodontal epithelium
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DOI：
10.1111/j.1600-0765.2011.01424.x
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发表时间：
2012-04-01
影响因子：
3.5
通讯作者：
Putnins, E. E.
中科院分区：
文献类型：
--
作者：
Fujita, T.;Firth, J. D.;Putnins, E. E.
背景和目的：上皮屏障是天然免疫的重要组成部分，对微生物的入侵具有保护作用。Claudin-1是一种紧密连接蛋白，已知与上皮细胞屏障有关。采用实验性大鼠牙周病模型，研究脂多糖对牙周炎大鼠牙周结合上皮细胞紧密连接相关分子基因表达的影响。材料与方法：将脂多糖作用于大鼠牙周沟8wk，激光捕获显微切割法采集牙周结合上皮细胞，进行基因芯片分析。结果：基因芯片分析证实，慢性脂多糖刺激可使牙周结合上皮细胞claudin-1基因表达降低。免疫组织化学分析证实，Claudin-1蛋白在交界上皮细胞中有表达，8wk的慢性内毒素局部应用显著降低了Claudin-1的表达。利用猪结合上皮细胞培养的Transwell模型验证了内毒素对Claudin-1蛋白表达的影响。内毒素刺激3wk后，牙周上皮屏障明显减少，并与claudin-1蛋白表达水平降低有关。结论：上述结果证实了实验性牙周病的发生与claudin-1基因和蛋白表达减少有关。这种关键紧密连接蛋白水平的降低可能导致屏障功能的破坏，并可能在牙周病的发生中发挥重要作用。
Background and Objective: The epithelial barrier is a critical component of innate immunity and provides protection against microbial invasion. Claudin-1, a tight junction protein, is known to contribute to the epithelial cell barrier. An experimentally induced rat periodontal disease model was used to study the effects of lipopolysaccharide (LPS) on the expression of tight junction-associated molecule genes in the junctional epithelium.Material and Methods: LPS was applied for 8 wk in the gingival sulcus, and junctional epithelium was collected by laser-capture microdissection and subjected to microarray analysis.Results: Microarray analysis identified that expression of the claudin-1 gene was decreased in the epithelium by chronic LPS challenge. Immunohistochemical analysis confirmed the expression of claudin-1 protein in junctional epithelium and that 8 wk of chronic LPS topical application significantly reduced claudin-1 expression. The effect of LPS on claudin-1 protein expression was validated using a porcine junctional epithelial cell culture Transwell model. The epithelial barrier, as measured using transmembrane resistance, was significantly reduced after 3 wk of LPS challenge and this was associated with a decreased level of expression of claudin-1 protein.Conclusion: These results confirm that the initiation of experimental periodontal disease is associated with reduction in the expression of claudin-1 gene and protein. This decreased level of a critical tight junction protein may result in the disruption of barrier function and may play an important role in the initiation of periodontal disease.