Irsogladine maleate regulates neutrophil migration and E-cadherin expression in gingival epithelium stimulated by Aggregatibacter actinomycetemcomitans
Irsogladine maleate regulates neutrophil migration and E-cadherin expression in gingival epithelium stimulated by Aggregatibacter actinomycetemcomitans
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DOI：
10.1016/j.bcp.2010.01.017
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发表时间：
2010-05-15
影响因子：
5.8
通讯作者：
Kurihara, Hidemi
中科院分区：
文献类型：
--
作者：
Fujita, Tsuyoshi;Kishimoto, Akiyoshi;Kurihara, Hidemi
马来酸伊索拉定 (IM) 可以对抗 Aggregatibacter actinomycetemcomitans 诱导的培养人牙龈上皮细胞 (HGEC) 中缝隙连接细胞间通讯的减少和 zonula occlusionns-1 的表达，这是一种主要的紧密连接结构蛋白。此外，IM 还可消除 Aaggregatibacter actinomycetemcomitans 诱导的 HGEC 中白细胞介素 (IL)-8 水平的增加。 HGEC、IM 中的连接复合物和趋化因子分泌可能有助于预防牙周病。为了阐明IM在体内外的作用和调节机制，我们检测了IM预处理下A放线菌诱导的E-cadherin表达和中性粒细胞趋化性。免疫组织化学研究表明，A放线菌应用于牙龈沟后，E-钙粘蛋白阳性细胞数量减少，细胞因子诱导的中性粒细胞趋化剂-2α（CINC-2）阳性细胞数量增加。 α）在大鼠牙龈上皮中。然而，在IM预处理的大鼠中，A放线菌的应用对牙龈上皮中的CINC-2α和E-钙粘蛋白影响不大。在培养的HGEC中，实时PCR和蛋白质印迹显示IM和ERK抑制剂PD98059消除了A放线菌引起的HGEC中CXCL-1和IL-8的增加。 p38 MAP激酶抑制剂SB203580恢复了E-钙粘蛋白表达的降低。此外，与未刺激的HGEC或IM预处理下伴放线菌刺激的HGEC的条件培养基相比，伴放线菌刺激的HGEC的条件培养基增强了人中性粒细胞趋化性。此外，IM 下调 A. actinomycetemcomitans 诱导的 p38 MAP 激酶和 ERK 磷酸化 总之，IM 可能通过调节牙龈上皮中中性粒细胞迁移和 E-cadherin 表达来控制 A. actinomycetemcomitans 诱导的牙龈炎症 (C) 2010 Elsevier Inc 保留所有权利
Irsogladine maleate (IM) counters Aggregatibacter actinomycetemcomitans-induced reduction of the gap junction intercellular communication and the expression of zonula occludens-1, which is a major tight junction structured protein, in cultured human gingival epithelial cells (HGEC) In addition, IM obviates the A actinomycetemcomitans-induced increase in interleukin (IL)-8 levels in HGEC Thus, by regulating the intercellular junctional complex and chemokine secretion in HGEC, IM may be useful to prevent periodontal disease. To clarify the effects and regulatory mechanism of IM in vivo and in vitro, we examined the expression of E-cadherin and neutrophil chemotaxis induced by A actinomycetemcomitans under IM pretreatment Immunohistochemical studies revealed that A actinomycetemcomitans application to the gingival sulcus decreased the number of cells positive for E-cadherin and increased those positive for cytokine-induced neutrophil chemoattractant-2 alpha (CINC-2 alpha) in rat gingival epithelium. However, in IM-pretreated rats, A actinomycetemcomitans application had little effect on CINC-2 alpha and E-cadherin in gingival epithelium In cultured HGEC, real-time PCR and Western blotting showed that IM and the ERK inhibitor PD98059 abolished the A actinomycetemcomitans-induced increase in CXCL-1 and IL-8 in HGEC On the other hand, IM, PD98059, and the p38 MAP kinase inhibitor SB203580 recovered the decrease in E-cadherin expression In addition, conditioned medium from A actinomycetemcomitans-stimulated HGEC enhanced human neutrophil chemotaxis, compared to that from un-stimulated HGEC or that from A actinomycetemcomitans-stimulated HGEC under IM pretreatment. Furthermore, IM down-regulated the p38 MAP kinase and ERK phosphorylations induced by A actinomycetemcomitans In conclusion, IM may control A. actinomycetemcomitans-induced gingival inflammation by regulating neutrophil migration and E-cadherin expression in gingival epithelium (C) 2010 Elsevier Inc All rights reserved