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

我们发现脐血中IL-18可作为早产儿脑损伤继发脑性瘫痪的生化标志物，而败血症是导致新生儿脑损伤的另一个因素。我们检测了IL-18和Toll样受体(TLR)配体之一的内毒素内毒素对人未成熟内皮细胞的影响。基因芯片分析表明，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，在脂多糖的诱导下表达。IL-18对一个细胞系的Lefty A有较强的诱导作用，对另一个细胞系有中度的诱导作用。我们还使用了CD34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细胞。脂多糖诱导Lefty A、IL8R和IL5RA的表达，IL-18促进几种趋化因子的表达。通过其他TLR配体的作用，Chomokine家族和ICAM基因的表达被诱导在恒定的水平上，但IL-18的表达水平在不同的细胞株之间是不同的。最近，有报道指出DNA多态在严重感染的临床表现上是不同的。综上所述，在早产儿中，严重的感染和高水平的血清IL-18可能通过TLR介导的信号对未成熟细胞造成损伤，DNA多态可能在改变对信号的敏感性方面发挥重要作用。

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.