Direct effects of IL-4/IL-13 and the nematode Nippostrongylus brasiliensis on intestinal epithelial cells in vitro
Direct effects of IL-4/IL-13 and the nematode Nippostrongylus brasiliensis on intestinal epithelial cells in vitro
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DOI：
10.1111/j.1365-3024.2010.01200.x
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发表时间：
2010-06-01
影响因子：
2.2
通讯作者：
Arizono, N.
中科院分区：
文献类型：
--
作者：
Takeda, K.;Hashimoto, K.;Arizono, N.
P>线虫感染诱导体内肠上皮细胞中粘蛋白和糖基化相关基因的上调。然而，在上皮细胞中诱导这些变化的因素尚未完全阐明。在本研究中，我们分析了Th 2细胞因子IL-4和IL-13和排泄分泌（ES）的产品的线虫Nippostrongylus brasiliensis上的主要粘蛋白核心肽MUC 2，唾液酸转移酶ST 3GalIV（Siat 4c）和硫转移酶HS 3ST 1在肠上皮来源的IEC-6细胞的基因表达的影响，通过定量逆转录（RT）-PCR。IL-4和IL-13的施用导致IEC-6细胞中ST 3GalIV和HS 3ST 1基因转录的显著上调，但对MUC 2没有影响。RT-PCR研究还证实了IL-13 R α 1和IL-4 R在IEC-6细胞中的组成型表达。另一方面，ES产物诱导ST 3GalIV的上调，但不诱导HS 3ST 1或MUC 2的上调，而IL-13和ES产物的共施用诱导MUC 2的轻微但显著的上调。活N.巴西蠕虫成虫与IEC-6细胞的共培养导致ST 3GalIV和MUC 2的上调。这些结果表明HS 3ST 1基因表达受到IL-4/IL-13的严格调节，而ST 3GalIV和MUC 2基因表达受到冗余机制的调节。
P>Nematode infections induce the upregulation of mucin- and glycosylation-related genes in intestinal epithelial cells in vivo. However, the factor(s) that induce these changes in epithelial cells have not been fully elucidated. In the present study, we analysed the effects of the Th2 cytokines IL-4 and IL-13 and the excretory-secretory (ES) product of the nematode Nippostrongylus brasiliensis on the gene expression of the major mucin core peptide MUC2, the sialyltransferase ST3GalIV (Siat4c) and the sulphotransferase HS3ST1 in intestinal epithelium-derived IEC-6 cells by quantitative reverse transcription (RT)-PCR. The administration of IL-4 and IL-13 resulted in a significant upregulation of ST3GalIV and HS3ST1 gene transcription, but had no effect on MUC2, in IEC-6 cells. RT-PCR studies also demonstrated the constitutive expression of IL-13R alpha 1 and IL-4R in IEC-6 cells. On the other hand, the ES product induced upregulation of ST3GalIV, but not HS3ST1 or MUC2, while coadministration of IL-13 and the ES product induced a slight but significant upregulation of MUC2. Co-incubation of live N. brasiliensis adult worms with IEC-6 cells resulted in the upregulation of ST3GalIV and MUC2. These results suggested that HS3ST1 gene expression is strictly regulated by IL-4/IL-13, while ST3GalIV and MUC2 gene expressions are regulated by redundant mechanisms.