Tu1294 EXOGENOUS L-FUCOSE PROTECTS THE INTESTINAL MUCOSAL BARRIER DEPENDING ON UP-REGULATION OF FUT2-MEDIATED FUCOSYLATION OF INTESTINAL EPITHELIAL CELLS IN DSS-INDUCED COLITIS MICE

Porcine epidemic diarrhea virus (PEDV) infects intestinal epithelial cells, destroys the intestinal mucosal barrier and then causes diarrhea in piglets. Glucagon-like peptide-2 (GLP-2) is a specific intestinal growth hormone that promotes the repair of damaged intestinal mucosa and improves the intestinal barrier. In this study, we investigated the functions of porcine GLP-2 gene in regulating PEDV infection. The intestinal tissues with damaged intestinal structures caused by PEDV infection were first confirmed and collected. Expression analysis indicated that the GLP-2 gene was expressed in the duodenum, jejunum and ileum tissues, and the mRNA level was significantly down-regulated in jejunum and ileum of piglets with damaged intestinal mucosa. Infection of PEDV to porcine small intestinal epithelial cells in vitro showed that GLP-2 gene was significantly decreased, which was consistent with the expression pattern in intestinal tissues. In addition, we silenced the GLP-2 gene by shRNA interfering and found that the copy numbers of PEDV were remarkably increased in the GLP-2 gene silencing cells. Our findings suggest that the GLP-2 gene was potentially involved in regulating PEDV infection and in maintaining the integrity of the intestinal mucosal barrier structure, which could contribute to our understanding of the mechanisms of PEDV pathogenesis and provide a theoretical basis for the identification and application of resistant genes in pig selective breeding for porcine epidemic diarrhea.

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Exogenous l ‐fucose protects the intestinal mucosal barrier depending on upregulation of FUT2‐mediated fucosylation of intestinal epithelial cells

The FASEB Journal ◽

10.1096/fj.202002446rrrr ◽

2021 ◽

Vol 35 (7) ◽

Author(s):

Ying Li ◽

Yudong Jiang ◽

Lei Zhang ◽

Wei Qian ◽

Xiaohua Hou ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Mucosal Barrier ◽

Intestinal Epithelial ◽

Intestinal Mucosal Barrier

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Free fucose is a danger signal to human intestinal epithelial cells

British Journal Of Nutrition ◽

10.1017/s0007114507812062 ◽

2008 ◽

Vol 99 (3) ◽

pp. 449-454 ◽

Cited By ~ 23

Author(s):

Wai Ling Chow ◽

Yuan Kun Lee

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Transforming Growth Factor ◽

Intestinal Epithelial Cells ◽

Direct Interaction ◽

Transforming Growth Factor Β ◽

Intestinal Lumen ◽

Mucosal Barrier ◽

Intestinal Epithelial ◽

Regulated Gene Expression

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 ofl-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-α, 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-β 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.

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Human β-defensin-3 reduces excessive autophagy in intestinal epithelial cells and in experimental necrotizing enterocolitis

Scientific Reports ◽

10.1038/s41598-019-56535-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Liping Chen ◽

Zhibao Lv ◽

Zhimei Gao ◽

Guijie Ge ◽

Xueli Wang ◽

...

Keyword(s):

Epithelial Cells ◽

Necrotizing Enterocolitis ◽

Rat Model ◽

Intestinal Epithelial Cells ◽

Critical Role ◽

Neonatal Rat ◽

Mucosal Barrier ◽

Intestinal Epithelial ◽

Barrier Dysfunction ◽

Autophagy Activity

AbstractNecrotizing enterocolitis (NEC) is a leading cause of mortality in preterm newborns. Intestinal barrier dysfunction is one key event in NEC pathogenesis. Human β-defensin-3 (hBD3), one member of cationic host defence peptides, was reported to reduce the development of necrotizing enterocolitis in a neonatal rat model. And autophagy was induced in the intestine of human and animals with NEC. We hypothesized that regulation of autophagy might play a critical role in hBD3-mediated protection against NEC injury. Autophagy activity was evaluated both in intestinal epithelial cells and in NEC models. Newborn Sprague-Dawley rats were divided randomly into four groups: Control + NS, Control + rapamycin, NEC + NS, and NEC + hBD3. Body weight, histological score, survival time, enterocyte migration and mucosal barrier were recorded. Our results showed that hBD3 pretreatment could effectively inhibit autophagy activity in cultured IEC-6 and Caco2 enterocytes, and CXCR4 might be involved in hBD3-mediated autophagy suppression. Moreover, hBD3-induced inhibition of autophagy significantly promoted the intestinal epithelial cell migration by wound healing assay and transwell migration assay. In the rat model of NEC, hBD3 could noticeably reduce the expression of autophagy-activated proteins, down-regulate the expression of inflammatory mediators, and promote the mucosal integrity. Our data suggest an additional role of hBD3-mediated protection against intestinal mucosal injury: inhibition of over-activated autophagy in enterocytes.

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Colostrum whey down-regulates the expression of early and late inflammatory response genes induced byEscherichia coliandSalmonella entericaTyphimurium components in intestinal epithelial cells

British Journal Of Nutrition ◽

10.1017/s0007114514003481 ◽

2014 ◽

Vol 113 (2) ◽

pp. 200-211 ◽

Cited By ~ 15

Author(s):

M. Blais ◽

M. Fortier ◽

Y. Pouliot ◽

S. F. Gauthier ◽

Y. Boutin ◽

...

Keyword(s):

Epithelial Cells ◽

Transcriptional Activation ◽

Inflammatory Responses ◽

Intestinal Epithelial Cells ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Bovine Colostrum ◽

Mucosal Barrier ◽

Intestinal Epithelial ◽

Inflammatory Genes

Pathogenic invasion byEscherichia coliandSalmonellaeremains a constant threat to the integrity of the intestinal epithelium and can rapidly induce inflammatory responses. At birth, colostrum consumption exerts numerous beneficial effects on the properties of intestinal epithelial cells and protects the gastrointestinal tract of newborns from pathogenic invasion. The present study aimed to investigate the effect of colostrum on the early and late inflammatory responses induced by pathogens. The short-term (2 h) and long-term (24 h) effects of exposure to heat-killed (HK)E. coliandSalmonella entericaTyphimurium on gene expression in the porcine intestinal epithelial cell (IPEC-J2) model were first evaluated by microarray and quantitative PCR analyses. Luciferase assays were performed using a NF-κB-luc reporter construct to investigate the effect of colostrum whey treatment on the activation of NF-κB induced by HK bacteria. Luciferase assays were also performed using NF-κB-luc, IL-8-luc and IL-6-luc reporter constructs in human colon adenocarcinoma Caco-2/15 cells exposed to dose–response stimulations with HK bacteria and colostrum whey. Bovine colostrum whey treatment decreased the expression of early and late inflammatory genes induced by HK bacteria in IPEC-J2, as well as the transcriptional activation of NF-κB-luc induced by HK bacteria. Unlike that with colostrum whey, treatment with other milk fractions failed to decrease the activation of NF-κB-luc induced by HK bacteria. Lastly, the reduction of the HK bacteria-induced activation of NF-κB-luc, IL-8-luc and IL-6-luc by colostrum whey was dose dependent. The results of the present study indicate that bovine colostrum may protect and preserve the integrity of the intestinal mucosal barrier in the host by controlling the expression levels of early and late inflammatory genes following invasion by enteric pathogens.

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Pyroptosis of Intestinal Epithelial Cells is Crucial to the Development of Mucosal Barrier Dysfunction and Intestinal Inflammation

Gastroenterology ◽

10.1016/s0016-5085(17)33282-1 ◽

2017 ◽

Vol 152 (5) ◽

pp. S967 ◽

Cited By ~ 1

Author(s):

Elisabeth M. Davis ◽

Yihong Kaufmann ◽

Hannah Goyne ◽

Yuxiu Wang ◽

Tsungyen Chen ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Inflammation ◽

Intestinal Epithelial Cells ◽

Mucosal Barrier ◽

Intestinal Epithelial ◽

Barrier Dysfunction

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Three-dimensional organization and functional relationships of endocytotic compartments in pig intestinal epithelial cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123283 ◽

1992 ◽

Vol 50 (1) ◽

pp. 576-577

Author(s):

Julian P. Heath ◽

Buford L. Nichols ◽

László G. Kömüves

Keyword(s):

Electron Microscopy ◽

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Three Dimensional ◽

Intestinal Epithelial ◽

Cell Surfaces ◽

Basal Surface ◽

Functional Relationships

The newborn pig intestine is adapted for the rapid and efficient absorption of nutrients from colostrum. In enterocytes, colostral proteins are taken up into an apical endocytotic complex of channels that transports them to target organelles or to the basal surface for release into the circulation. The apical endocytotic complex of tubules and vesicles clearly is a major intersection in the routes taken by vesicles trafficking to and from the Golgi, lysosomes, and the apical and basolateral cell surfaces.Jejunal tissues were taken from piglets suckled for up to 6 hours and prepared for electron microscopy and immunocytochemistry as previously described.

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