Mobilization of TLR4 Into Lipid Rafts by Aggregatibacter Actinomycetemcomitans in Gingival Epithelial Cells
Mobilization of TLR4 Into Lipid Rafts by Aggregatibacter Actinomycetemcomitans in Gingival Epithelial Cells
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DOI：
10.1159/000447877
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Kurihara, Hidemi
中科院分区：
文献类型：
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作者：
Imai, Haruka;Fujita, Tsuyoshi;Kurihara, Hidemi
背景资料：通过微生物刺激牙龈上皮细胞产生炎症细胞因子的机制的调查可能会提供深入了解牙周炎的发病机制。脂筏是细胞膜上的微区，包含大量的受体，并主要参与信号转导。我们在此研究了脂筏参与牙周病原体刺激牙龈上皮细胞表达白细胞介素（IL-6）和IL-8。研究方法：在甲基-β-环糊精（M β CD）存在下，用伴放线菌聚集杆菌或肿瘤坏死因子（TNF）-α刺激人牙龈细胞系OBA 9。结果：A.放线菌共生菌或TNF-α。增加OBA 9细胞IL-8和IL-6 mRNA水平，促进ERK和p38 MAP激酶磷酸化。M β CD预处理可抑制A.放线菌共生菌，但不抑制TNF-α诱导的反应。TLR 4的转染抑制了放线菌伴放线菌引起的IL-8和IL-6 mRNA水平的升高。共聚焦显微镜显示，M β CD抑制TLR 4进入脂筏的动员。结论：TLR 4进入脂筏参与A.伴放线菌(C)2016作者（s）由S. Karger AG，巴塞尔
Background: An investigation of the mechanisms underlying the production of inflammatory cytokines through the stimulation of microorganisms on gingival epithelial cells may provide insights into the pathogenesis of the initiation of periodontitis. Lipid rafts, microdomains in the cell membrane, include a large number of receptors, and are centrally involved in signal transduction. We herein examined the involvement of lipid rafts in the expression of interleukin (IL-6) and IL-8 in gingival epithelial cells stimulated by periodontal pathogens. Methods: OBA9, a human gingival cell line, was stimulated by Aggregatibacter actinomycetemcomitans or tumor necrosis factor (TNF)-alpha in the presence of methyl-beta-cyclodextrin (M beta CD). Results: A. actinomycetemcomitans or TNF-alpha. increased IL-8 and IL-6 mRNA levels, and promoted the phosphorylation of ERK and p38 MAP kinase in OBA9. The pretreatment with M beta CD abolished increases in IL-6 and IL-8 mRNA levels and the phosphorylation induced by A. actinomycetemcomitans, but did not suppress the response induced by TNF-alpha. The transfection of TLR4 inhibited A, actinomycetemcomitans-induced increases in IL-8 and IL-6 mRNA levels. Confocal microscopy revealed that M beta CD inhibited the mobilization of TLR4 into lipid rafts. Conclusion: The mobilization of TLR4 into lipid rafts is involved in the expression of inflammatory cytokines and phosphorylation of MAP kinase in human gingival epithelial cells stimulated by A. actinomycetemcomitans. (C) 2016 The Author(s) Published by S. Karger AG, Basel