Gene expression in the model system of neonatal brain damage with increased levels of serum IL-18

血清IL-18水平升高的新生儿脑损伤模型系统中的基因表达

• 批准号: 17591764
• 负责人: HASHIMOTO Tomoko
• 金额: $ 2.24万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591764/
• 关键词: IL-18; endothelial cells; stem cells; toll-like receptor; cDNA microarray; 未熟児; 脳性麻痺; 臍帯血; 敗血症; TGF-β

We found that IL-18 in cord blood serves as a biochemical marker of brain damages followed by cerebral palsy in premature infants, and sepsis is another factor to induce neonatal brain damages. We examined the effects of IL-18 and endotoxin LPS, one of the toll-like receptor(TLR) ligands, to human immature endothelial cells. The cDNA microarray analysis showed that the expression of several chemokine and receptor genes and the endometrial bleeding associated factor gene, also known as Lefty-A, was induced by LPS. Lefty A was highly induced by IL-18 in one cell line but moderately in the other. We also used CD34-positive human hair follicle-derived stem cells that can differentiate to keratinocytes and neuronal cells. LPS induced the expression of Lefty A, IL8R and IL5RA, and IL-18 enhanced the expression of several chemokines. By treatment with other TLR ligands, the expression of the chomokine family and the ICAM genes were induced at a constant level, but the expression levels of IL-18 were variable among cell strains.Recently, several reports noted that DNA polymorphisms vary clinical manifestations of severe infection. Taken together, in premature infants, severe infection and high serum IL-18 may cause damages to immature cells probably through TLR-mediated signals, and DNA polymorphisms may play an important role to modify the sensitivity to the signals.

我们发现，脐血中的IL-18可作为早产儿脑性瘫痪后脑损伤的生化标志物，败血症是导致新生儿脑损伤的另一个因素。我们研究了IL-18和内毒素LPS（Toll样受体（TLR）配体之一）对人未成熟内皮细胞的作用。cDNA微阵列分析显示，LPS可诱导几种趋化因子和受体基因以及子宫内膜出血相关因子基因（也称为Lefty-A）的表达。在一个细胞系中，IL-18高度诱导Lefty A，但在另一个细胞系中中度诱导Lefty A。我们还使用了CD 34阳性的人毛囊来源的干细胞，可以分化为角质形成细胞和神经元细胞。LPS诱导Lefty A、IL 8 R和IL 5 RA的表达，并且IL-18增强几种趋化因子的表达。通过与其他TLR配体的治疗，chomokine家族和ICAM基因的表达诱导在一个恒定的水平，但IL-18的表达水平是可变的细胞strain.Recently，一些报告指出，DNA多态性不同的严重感染的临床表现。总之，在早产儿中，严重感染和高血清IL-18可能通过TLR介导的信号对未成熟细胞造成损伤，并且DNA多态性可能在改变对信号的敏感性方面起重要作用。