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Analysis of signaling via Toll-like receptors in Kawasaki disease

川崎病中 Toll 样受体信号传导分析

基本信息

批准号：
18591158
负责人：
NISHIMURA Shinji
金额：
$ 1.79万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Kawasaki disease (KD) is an acute febrile illness in childhood characterized by the formation of aneurysms in coronary arteries. It is believed that KD is caused by infectious agents because of its epidemic waves and high incidence of familial occurrence. Because an increase in the levels and dysfunction of B cells in peripheral blood was reported in KD, we investigated the expression of cluster of differentiation 180 (CD180), a toll-like receptor homologue, in the B cells of children with KD, and in those with bacterial or viral infections. The percentages of CD180 positive B cells were significantly higher in children with KD or viral infections than in those with bacterial infections or in healthy controls (P<0.05). When the expression levels of CD180 were compared by using the mean fluorescent intensity (MFI) ratio of patients to bacterial infection (0.841 ± 0.315), the level of CD180 expression was also significantly up-regulated in children with KD (1.366±0.443 : P=0.0072) or viral infections (1.391± 0.307 : P=0.0191). To clarify the effect of viral infection on the expression of CD180, B cells were stimulated with poly inosinic-cytidyric acid [poly (IC)], a. synthetic double-stranded RNA. Poly(IC) clearly enhanced CD180 expression in B cells in vitro, both at the protein and messenger RNA levels. The association between the CD180 expression and several risk factors for CAL formation, none of risk factors were associated with the expression level of CD180. But the percentage of CD180 positive B cells was extremely high in KD patients displaying CAL formation. These results suggest that similar mechanisms may be involved in the up-regulation of B cell CD180 expression in patients with either KD or viral infections

川崎病（KD）是一种儿童期急性发热性疾病，其特征是冠状动脉形成动脉瘤。由于川崎病呈流行趋势且家族发病率高，人们认为川崎病是由传染源引起的。由于川崎病患者外周血中 B 细胞的水平增加和功能障碍，我们研究了分化簇 180 (CD180)（一种 Toll 样受体同源物）在川崎病儿童以及细菌或病毒感染儿童 B 细胞中的表达情况。川崎病或病毒感染儿童的CD180阳性B细胞百分比显着高于细菌感染儿童或健康对照（P<0.05）。当用患者与细菌感染的平均荧光强度（MFI）比（0.841±0.315）比较CD180的表达水平时，KD（1.366±0.443：P=0.0072）或病毒感染（1.391±0.307：P=0.0191）儿童的CD180表达水平也显着上调。为了阐明病毒感染对 CD180 表达的影响，用聚肌苷胞苷酸 [poly (IC)] 刺激 B 细胞，a。合成双链RNA。 Poly(IC) 在体外明显增强 B 细胞中蛋白质和信使 RNA 水平的 CD180 表达。 CD180表达与CAL形成的几个危险因素之间的关联，没有任何危险因素与CD180的表达水平相关。但在显示 CAL 形成的 KD 患者中，CD180 阳性 B 细胞的百分比极高。这些结果表明，类似的机制可能与 KD 或病毒感染患者的 B 细胞 CD180 表达上调有关