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

肠道线虫感染诱导明显的杯状细胞增生和粘液分泌，但其作用和调节机制尚不完全清楚。本研究旨在阐明线虫感染后上皮粘液产生的调控机制。逆转录(RT)-real - time PCR检测巴西尼波圆线虫感染大鼠肠上皮细胞的基因表达结果显示，mucin核心肽（MUC） 2、唾液基转移酶（Siat） 4c和三叶因子家族（TFF） 3早在感染后2-4天就出现上调，提示它们与早期的先天保护反应有关。感染后7天及以后，当线虫性成熟时，MUC3、MUC4、抵抗素样分子β (relm - β)和30-硫转移酶（3ST）1基因显著上调。肥大细胞缺陷的Ws/Ws大鼠中也观察到类似的糖基化相关基因表达的改变，而胸腺功能不全的rnu/rnu大鼠中，relm - β、Siat4c和3ST1的表达水平明显低于+/+大鼠。利用大鼠肠细胞系IEC-6进行的体外研究表明，Siat4c和3ST1基因的表达在IL-4和/或IL-13的作用下显著上调，表明Siat4c和3ST1基因的表达受Th2细胞因子的调控。同样，在感染多回Heligmosomoides线虫的免疫缺陷小鼠中，Siat4c基因表达显著低于+/+小鼠。综上所述，这些结果表明Th2细胞因子通过上调肠上皮细胞Siat4c和3ST1的表达，在调节粘蛋白和膜糖蛋白末端糖链中起重要作用。

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.