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人胎儿肠成纤维细胞对脂多糖刺激高度敏感

奥克布尔-沃诺迪,AC;李,G;阿南德,B;卢吉娜,IG;

肠道肌成纤维细胞有助于炎症性肠病成人的免疫调节,但尚未在新生儿肠道炎症性疾病中表现出来。比较脂多糖(LPS)刺激的白细胞介素-8 (IL-8)在体外培养的人胎儿和成熟肠肌成纤维细胞之间的产生。增加浓度的大肠杆菌LPS刺激胎儿、新生儿和成人细胞。在LPS刺激的胎儿肌成纤维细胞中,通过real-time PCR检测toll样受体4 mRNA的表达,并用抗toll样受体4抗体检测toll样受体4受体活性。用化学抑制剂和蛋白印迹法评估丝裂原激活蛋白激酶途径的活性。ELISA定量检测IL-8的产生。LPS刺激胎儿肌成纤维细胞产生IL-8呈剂量依赖性。toll样受体4的表达是构成性的,toll样受体4受体阻断使IL-8的产生降低42% (P=0.0262)。C-Jun n端激酶、p38和NF-B抑制剂显著减弱LPS刺激的IL-8产生,分别降低42%、33%和2%。丝裂原激活蛋白激酶的活性通过蛋白印迹法证实。 These data demonstrate increased IL-8 production by foetal myofibroblasts that is partially mediated by Toll-like receptor 4, mitogen activated protein kinase and NF-B cell signalling pathways. Intestinal myofibroblasts cells may contribute to the dysregulated inflammatory response in the immature intestine and may form targets that lead to new therapies to prevent neonatal intestinal inflammatory bowel diseases.

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