Chow Wai Ling, Lee Yuan Kun
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, MD4 A, Singapore 117597, Singapore.
Br J Nutr. 2008 Mar;99(3):449-54. doi: 10.1017/S0007114507812062. Epub 2007 Aug 13.
Fucose is present in foods, and it is a major component of human mucin glycoproteins and glycolipids. l-Fucose can also be found at the terminal position of many cell-surface oligosaccharide ligands that mediate cell-recognition and adhesion-signalling pathways. Mucin fucose can be released through the hydrolytic activity of pathogens and indigenous bacteria, leading to the release of free fucose into the intestinal lumen. The immunomodulating effects of free fucose on intestinal epithelial cells (enterocyte-like Caco-2) were investigated. It was found that the presence of l-fucose up regulated genes and secretion of their encoded proteins that are involved in both the innate and adaptive immune responses, possibly via the toll-like receptor-2 signalling pathway. These include TNFSF5, TNFSF7, TNF-alpha, IL12, IL17 and IL18. Besides modulating immune reactions in differentiated Caco-2 cells, fucose induced a set of cytokine genes that are involved in the development and proliferation of immune cells. These include the bone morphogenetic proteins (BMP) BMP2, BMP4, IL5, thrombopoietin and erythropoietin. In addition, the up regulated gene expression of fibroblast growth factor-2 may help to promote epithelial cell restitution in conjunction with the enhanced expression of transforming growth factor-beta mRNA. Since the exogenous fucose was not metabolised by the differentiated Caco-2 cells as a carbon source, the reactions elicited were suggested to be a result of the direct interaction of fucose and differentiated Caco-2 cells. The presence of free fucose may signal the invasion of mucin-hydrolysing microbial cells and breakage of the mucosal barrier. The intestinal epithelial cells respond by up regulation and secretion of cytokines, pre-empting the actual invasion of pathogens.
岩藻糖存在于食物中，它是人类黏蛋白糖蛋白和糖脂的主要成分。L-岩藻糖也可在许多介导细胞识别和黏附信号通路的细胞表面寡糖配体的末端位置找到。黏蛋白岩藻糖可通过病原体和原生细菌的水解活性释放出来，导致游离岩藻糖释放到肠腔中。研究了游离岩藻糖对肠上皮细胞（肠上皮样Caco-2细胞）的免疫调节作用。发现L-岩藻糖的存在上调了参与先天性和适应性免疫反应的基因及其编码蛋白的分泌，可能是通过Toll样受体-2信号通路。这些包括TNFSF5、TNFSF7、肿瘤坏死因子-α、白细胞介素12、白细胞介素17和白细胞介素18。除了调节分化的Caco-2细胞中的免疫反应外，岩藻糖还诱导了一组参与免疫细胞发育和增殖的细胞因子基因。这些包括骨形态发生蛋白（BMP）BMP2、BMP4、白细胞介素5、血小板生成素和促红细胞生成素。此外，成纤维细胞生长因子-2基因表达的上调可能有助于促进上皮细胞修复，同时转化生长因子-β mRNA的表达增强。由于分化的Caco-2细胞没有将外源性岩藻糖作为碳源进行代谢，因此认为引发的反应是岩藻糖与分化的Caco-2细胞直接相互作用的结果。游离岩藻糖的存在可能表明黏蛋白水解微生物细胞的入侵和黏膜屏障的破坏。肠上皮细胞通过上调和分泌细胞因子做出反应，从而先发制人地应对病原体的实际入侵。
