Irsogladine maleate abolishes the increase in interleukin-8 levels caused by outer membrane protein 29 from Aggregatibacter (Actinobacillus) actinomycetemcomitans through the ERK pathway in human gingival epithelial cells
Irsogladine maleate abolishes the increase in interleukin-8 levels caused by outer membrane protein 29 from Aggregatibacter (Actinobacillus) actinomycetemcomitans through the ERK pathway in human gingival epithelial cells
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DOI：
10.1111/j.1600-0765.2007.01059.x
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发表时间：
2008-10-01
影响因子：
3.5
通讯作者：
Kurihara, H.
中科院分区：
文献类型：
--
作者：
Kishimoto, A.;Fujita, T.;Kurihara, H.
背景与目的：马来酸伊索拉定(Irsogladine Maleate，IM)可抑制外膜蛋白(OMP)29诱导的伴生放线菌(Aggregatibacter，Aggregatibacter)伴生放线菌在人牙龈上皮细胞(HGEC)培养中产生IL-8。然而，IM如何抑制OMP29诱导的IL-8表达的增加仍不清楚。本研究从细胞内信号转导途径入手，探讨其抑制作用的机制。材料和方法：将细胞内信号分子抑制剂预先处理的HGEC分别加入OMP29(1 mU g/mL)和IM(1 MU M)。用实时定量聚合酶链式反应和酶联免疫吸附试验分别检测IL-8在mRNA和蛋白水平的表达。结果：细胞外信号调节激酶(ERK)抑制剂PD98059和IM可阻断OMP29诱导的HGEC IL-8水平的升高。Jun激酶抑制剂SP600125和核因子kappaB抑制剂PDTC不影响OMP29诱导的IL-8mRNA表达的增加。OMP29可刺激HGEC中ERK的磷酸化。结论：IM抑制HGEC中ERK的磷酸化，最终抑制OMP29诱导的IL-8的升高。
Background and Objective: Irsogladine maleate (IM) suppresses the increase in interleukin (IL)-8 production induced by outer membrane protein (OMP) 29 from Aggregatibacter (Actinobacillus) actinomycetemcomitans in cultures of human gingival epithelial cells (HGEC). However, how IM suppresses the OMP29-induced increase in IL-8 expression remains unknown. In this study, we focused on intracellular signaling pathways to elucidate the mechanism behind the suppression.Material and Methods: HGEC, which had been pretreated with inhibitors of intracellular signaling molecules, were exposed to OMP29 (1 mu g/mL) with or without IM (1 mu M). IL-8 expression at the mRNA and protein levels was examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Extracellular signal-regulated kinase (ERK) activity was measured with a p44/42 mitogen-activated protein kinase assay kit.Results: An ERK inhibitor, PD98059, as well as IM, obviated the OMP29-induced increase in IL-8 levels in HGEC. A Jun kinase inhibitor, SP600125, and a nuclear factor kappa B inhibitor, PDTC, did not influence the OMP29-induced increase in IL-8 mRNA expression. The OMP29 stimulated phosphorylation of ERK in HGEC. Irsogladine maleate inhibited the phosphorylation.Conclusion: The suppression of the phosphorylation of ERK by IM in HGEC culminates in inhibition of the OMP29-induced increase in IL-8.