Regulation mechanisms of the intestinal mucins and their core peptides and the role of mucins in mucosal immunity against nematode infections.

肠道线虫感染可诱导杯状细胞增生和粘液分泌，但其作用和调控机制尚未完全清楚。本研究旨在阐明线虫感染后上皮粘液产生的调控机制。利用逆转录-实时荧光PCR技术研究了巴西日本圆线虫感染大鼠肠上皮细胞的基因表达，结果表明，粘蛋白核心肽（MUC）2、唾液酸转移酶（Siat）4c和三叶因子家族（TFF）3在感染后2-4 d即表达上调，提示它们与早期先天性保护反应有关。感染后7天，此后，当线虫达到性成熟，MUC 3，MUC 4，抵抗素样分子β（Relm-beta）和30-磺基转移酶（3ST）1基因表现出显着的上调。在肥大细胞缺陷的Ws/Ws大鼠中也观察到糖基化相关基因表达的类似改变，而在无胸腺rnu/rnu大鼠中，Relm-β、Siat 4c和3ST 1的表达水平显著低于+/+大鼠。使用大鼠肠细胞系IEC-6的体外研究表明，Siat 4c和3ST 1基因表达响应于IL-4和/或IL-13的施用而显著上调，表明唾液酸转移酶和磺基转移酶的表达受Th 2细胞因子调节。类似地，在感染多脑Heligmosomoides线虫的免疫缺陷scid小鼠中，Siat 4c基因表达显著低于+/+小鼠。总之，这些结果表明，Th 2细胞因子通过上调肠上皮细胞中Siat 4c和3ST 1的表达，在调节粘蛋白和膜糖蛋白的末端糖链中具有重要作用。

Intestinal nematode infections induce marked goblet cell hyperplasia and mucus secretion, but its role and regulation mechanisms have not been fully understood. The present study aimed at elucidation of the regulation mechanisms of the epithelial mucus production after nematode infections. The gene expression of rat intestinal epithelial cells during infection with the nematode Nippostrongylus brasiliensis studied by reverse transcription (RT)-realtime PCR showed that mucin core peptide (MUC) 2, sialyltransferase (Siat) 4c and trefoil factor family (TFF) 3 were upregulated as early as 2-4 days post-infection, suggesting that they are associated with an early innate protective response. Seven days after infection and thereafter, when nematodes reached the sexual maturity, MUC3, MUC4, resistin-like molecule beta (Relm-beta) and 30-sulfotransferase (3ST)1 genes exhibited marked upregulation. Similar alterations of glycosylation-related gene expression were also observed in mast-cell-deficient Ws/Ws rats, while in athymic rnu/rnu rats, expression levels of Relm-beta, Siat4c and 3ST1 were significantly lower than in +/+ rats. In vitro studies using the rat intestinal cell-line, IEC-6, showed that Siat4c and 3ST1 gene expression was significantly upregulated in response to the administration of IL-4 and/or IL-13, indicating that the expression of the sialyl-and sulfo-transferases is regulated by Th2 cytokines. Similarly, in immune-deficient scid mice infected with the nematode Heligmosomoides polygyrus, Siat4c gene expression was significantly lower than in +/+ mice. Overall, these results suggested that Th2 cytokines have an important role in the modulation of terminal sugar chains of mucin and membrane glycoprotein via the upregulation of Siat4c and 3ST1 expression in intestinal epithelial cells.