Correlation between increased levels of serum IL-18 and high frequency of neonatal brain damage

血清IL-18水平升高与新生儿脑损伤高频率之间的相关性

• 批准号: 14571593
• 负责人: HASHIMOTO-TAMAOKI Tomoko
• 金额: $ 2.18万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571593/
• 关键词: IL-18; Neuronal differentiation; Cell damage; Transcription activity; Brain damage; Premature infant; 未熟児脳障害; 胚性細胞; 神経分化阻害; アポトーシス; プロモーター活性; レチノイン酸

To clarify the role of the high concentration of IL-18 to develop cerebral palsy in premature infants, we used mouse P19 embryonal carcinoma cells as a model for early neuronal differentiation. During differentiation of P19 cells, increased expression of IL-18mRNA transcribed from the first exon and IL-18 precursor protein was observed. However, exogenous mature IL-18 (active form) showed no effects on cell damage or neuronal differentiation. We then examined whether exogenous mature IL-18 influences human immature endothelial cells. cDNA microarray analysis showed that several genes were up- or down-regulated, suggesting that mature IL-18 may target immature endothelial cells, resulting in severe brain damages.

为了阐明高浓度IL-18在早产儿脑瘫发生中的作用，我们使用小鼠P19胚胎癌细胞作为早期神经元分化的模型。在P19细胞分化过程中，第一外显子转录的IL-18mRNA和IL-18前体蛋白表达增加。然而，外源性成熟IL-18(活性形式)对细胞损伤或神经元分化没有影响。然后，我们研究了外源性成熟IL-18是否影响未成熟的人内皮细胞。基因芯片分析显示，有几个基因表达上调或下调，提示成熟的IL-18可能针对未成熟的内皮细胞，导致严重的脑损伤。