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血清可溶性 E-钙黏蛋白在 Q 热患者中的高浓度。

High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever.

机构信息

Aix-Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France.

APHM, IHU-Méditerranée Infection, UF Immunologie, Marseille, France.

出版信息

Front Cell Infect Microbiol. 2019 Jun 21;9:219. doi: 10.3389/fcimb.2019.00219. eCollection 2019.

Abstract

Cadherins switching is a hallmark of neoplasic processes. The E-cadherin (E-cad) subtype is one of the surface molecules regulating cell-to-cell adhesion. After its cleavage by sheddases, a soluble fragment (sE-cad) is released that has been identified as a pro-carcinogenic inflammatory signal in several bacteria-induced cancers. Recently we reported that Q fever, a disease due to infection, can be complicated by occurrence of non-Hodgkin lymphoma (NHL). Therefore, we studied E-cad switching in Q fever. The sE-cad levels were found increased in the sera of acute and persistent Q fever patients, whereas they remained at the baseline in controls groups of healthy donors, people cured of Q fever, patients suffering from unrelated inflammatory diseases, and past Q fever patients who developed NHL. These results indicate that sE-cad can be considered as a new biomarker of infection rather than a marker of NHL-associated to Q fever. We wondered if changes in sE-cad reflected variations in the gene transcription. The expression of E-cad mRNA and its intracellular ligand β-catenin was down-regulated in peripheral blood mononuclear cells (PBMCs) of patients with either acute or persistent forms of Q fever. Indeed, a lower cell-surface expression of E-cad was measured in a minority (<5%) subpopulation of HLADR/CD16 monocytes from patients with acute Q fever. However, a very strong increase in E-cad expression was observed on more than 30% of the HLADR/CD16 monocytes of persistent Q fever patients, a cell subpopulation known to be a target for in humans. An experimental infection of healthy donors' PBMCs with , was performed to directly evaluate the link between interaction with PBMCs and their E-cad expression. A significant increase in the percentage of HLADR/CD16 monocytes expressing E-cad was measured after PBMCs had been incubated for 8 h with Nine Mile strain. Altogether, these data demonstrate that severely impairs the E-cad expression in circulating cells of Q fever patients.

摘要

钙黏蛋白转换是肿瘤发生过程的一个标志。E-钙黏蛋白(E-cad)亚型是调节细胞间黏附的表面分子之一。在被脱落酶切割后,释放出可溶性片段(sE-cad),已被鉴定为几种细菌诱导的癌症中的致癌前炎症信号。最近我们报道称,Q 热,一种由 感染引起的疾病,可能会因非霍奇金淋巴瘤(NHL)的发生而变得复杂。因此,我们研究了 Q 热中的 E-cad 转换。在急性和持续性 Q 热患者的血清中发现 sE-cad 水平升高,而在健康供体、治愈 Q 热的患者、患有无关炎症性疾病的患者和曾患有 Q 热但发展为 NHL 的患者的对照组中,sE-cad 水平保持在基线水平。这些结果表明,sE-cad 可以被认为是 感染的一个新的生物标志物,而不是与 Q 热相关的 NHL 标志物。我们想知道 sE-cad 的变化是否反映了 基因转录的变化。在急性或持续性 Q 热患者的外周血单核细胞(PBMCs)中,E-cadmRNA 及其细胞内配体β-连环蛋白的表达下调。实际上,在急性 Q 热患者中,少数(<5%)HLADR/CD16 单核细胞亚群中测量到 E-cad 的细胞表面表达降低。然而,在持续性 Q 热患者的 HLADR/CD16 单核细胞中,超过 30%的细胞观察到 E-cad 表达的强烈增加,这是人类中 感染的一个已知靶点的细胞亚群。对健康供体的 PBMC 进行了 感染实验,以直接评估 与 PBMC 相互作用及其 E-cad 表达之间的联系。在 PBMC 与九英里株孵育 8 小时后,测量到表达 E-cad 的 HLADR/CD16 单核细胞的百分比显著增加。总之,这些数据表明,严重损害了 Q 热患者循环细胞中的 E-cad 表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a77/6598114/a34b40d84dfb/fcimb-09-00219-g0001.jpg

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