Tumor necrosis factor α is a key modulator of inflammation in cerebral aneurysms
Tumor necrosis factor α is a key modulator of inflammation in cerebral aneurysms
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DOI：
10.1227/01.neu.0000170439.89041.d6
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发表时间：
2005-09-01
期刊：
影响因子：
4.8
通讯作者：
Berenstein, A
中科院分区：
文献类型：
--
作者：
Jayaraman, T;Berenstein, V;Berenstein, A
目的：虽然颅内动脉瘤（IA）是美国的一个主要公共卫生问题，但已知的病因很少。大多数动脉瘤在破裂之前一直没有症状，导致蛛网膜下腔出血，这是最严重的中风形式之一。尽管血管内和显微外科治疗的技术进步，这些患者仍然有很高的死亡率和发病率。因此，动脉瘤形成和生长的生物学是非常感兴趣的。人IA组织中T和B淋巴细胞以及巨噬细胞的存在表明炎症在IA发病机制中的作用。然而，在脑动脉瘤形成和生长过程中参与和调节的细胞因子的类型尚不清楚。为了研究IA的潜在发病机制，我们分析了参与促炎和抗炎反应的细胞因子的表达。方法：聚合酶链反应被用来评估细胞因子和凋亡调节因子Fas相关死亡结构域蛋白的相对信使核糖核酸表达水平。Western blot分析被用来确定这些基因的蛋白质表达。结果：我们发现，促炎细胞因子，肿瘤坏死因子及其促凋亡的下游目标，Fas相关的死亡结构域蛋白，在人类动脉瘤增加。相比之下，白细胞介素10，这是分泌主要由辅助性T细胞2，是缺乏动脉瘤。聚合酶链反应衍生的基因表达数据进行了确认，通过Western blotting使用特定antibodies. CONCLUSION：增加肿瘤坏死因子和Fas相关的死亡结构域蛋白可能有有害的主要和次要的影响，通过促进炎症和随后的血管和免疫细胞凋亡，从而削弱血管壁对脑动脉。
OBJECTIVE: Although intracranial aneurysms (IAs) are a major public health problem in the United States, few etiological factors are known. Most aneurysms remain asymptomatic until they rupture, producing subarachnoid hemorrhage, one of the most severe forms of stroke. Despite the technical advances in endovascular and microsurgical treatment, these patients still have high mortality and morbidity rates. Hence, the biology of aneurysm formation and growth is of intense interest. The presence of T and B lymphocytes, as well as macrophages, in human IA tissues suggests a role for inflammation in IA pathogenesis. However, the types of cytokines that are involved and regulated during cerebral aneurysm formation and growth are not known. To study the underlying pathogenesis of IA, we analyzed the expression of cytokines that participate in proinflammatory and anti-inflammatory responses.METHODS: Polymerase chain reaction was used to assess relative messenger ribonucleic acid expression levels of cytokines and an apoptotic modulator, Fas-associated death domain protein. Western blot analysis was used to determine protein expression from these genes.RESULTS: We show that the proinflammatory cytokine, tumor necrosis factor a and its proapoptotic downstream target, Fas-associated death domain protein, are increased in human aneurysms. In contrast, interleukin 10, which is secreted predominantly by T helper 2 cells, was absent in aneurysms. Polymerase chain reaction-derived gene expression data were confirmed by Western blotting using specific antibodies.CONCLUSION: Increased tumor necrosis factor a and Fas-associated death domain protein may have deleterious primary and secondary effects on cerebral arteries by promoting inflammation and subsequent apoptosis in vascular and immune cells, thereby weakening vessel walls.