Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis

Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis
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DOI:
10.1016/j.lfs.2009.03.001
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发表时间:
2009-05-22
期刊:
影响因子:
6.1
通讯作者:
Rossa, Carlos, Jr.
Rossa, Carlos, Jr.
中科院分区:
医学2区
文献类型:
--
作者:
de Aquino, Sabrina Garcia;Manzolli Leite, Fabio Renato;Rossa, Carlos, Jr.

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目的:评价两种实验性牙周炎模型中炎症介质激活相关的信号通路。主要方法:采用脂多糖(LPS)注射和结扎两种模型。使用Wistar大鼠,每周两次将30 μ g来自大肠杆菌的LIPS注射到上磨牙的腭侧。在第一磨牙周围进行结扎。对照组在腭牙龈上接受PBS注射,而在下磨牙上不放置结扎线。主要发现:结扎模型与细胞外调节激酶(ERK)和p38丝裂原活化蛋白激酶(MAPK)以及核因子κ B(NF-κ B)的快速和短暂激活有关。LPS模型中这些信号通路的激活被延迟,但在整个30天的实验期间持续。两种模型诱导的炎症变化相似;然而,结扎模型的炎症程度显著降低,这抵消了在信号传导通路活化上观察到的降低。激活信号转导子和转录激活子(SEAT)-3酪氨酸残基和SPAT-5的磷酸化,观察到只有在连接model.Significance:调节基因表达的结果从激活的信号转导途径启动受体配体结合的外部抗原,也由宿主免疫系统产生的细胞因子。了解与特定疾病相关的信号通路可能为新的治疗方法提供有用的信息。(C)2009 Elsevier Inc. All rights reserved.
Aims: Evaluate the signaling pathways associated with inflammatory mediators activated in two models of experimental periodontitis.Main methods: Two models were used: lipopolysaccharide (LPS) injections and ligature placement. Wistar rats were used and 30 mu g LIPS from Escherichia coli was injected twice a week into the palatal aspect of the upper molars. Ligatures were placed around lower first molars. A control group received injections of PBS on the palatal gingivae whereas no ligatures were placed on the lower molars. Samples were collected 5,15 and 30 days and processed for analysis by Western blotting and stereometry.Key findings: The ligature model was associated with rapid and transient activation of extracellular-regulated kinases (ERK) and p38 mitogen-activated protein kinase (MAPK) as well as of nuclear factor kappa B (NF-kappa B). Activation of these signaling pathways on the LPS model was delayed but sustained throughout the 30-day experimental period. Inflammatory changes induced by both models were similar; however there was a significant reduction on inflammation degree on the ligature model, which paralleled the decrease observed on the activation of the signaling pathways. Activation of signal transducer and activator of transcription (SEAT)-3 by phosphorylation of Tyrosine residues and of SPAT-5 was observed only on the ligature model.Significance: Regulation of gene expression results from the activation of signaling pathways initiated by receptor-ligand binding of external antigens and also of cytokines produced by the host immune system. Understanding the signaling pathways relevant fora given condition may provide information useful for novel therapeutic approaches. (C) 2009 Elsevier Inc. All rights reserved.