Free fucose is a danger signal to human intestinal epithelial cells.
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.
Chow
Wai Ling
WL
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, MD4 A, Singapore 117597, Singapore.
Lee
Yuan Kun
YK
D018938:Caco-2 Cells; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005643:Fucose / Q000276:immunology* / Q000493:pharmacokinetics; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D005643:Fucose