ENDOPLASMIC RETICULUM STRESS ENHANCES THE RELEASE OF SERINE PROTEASES BY EPITHELIAL CELLS ALTERING THE INTESTINAL BARRIER FUNCTION

As the largest interface between the outside and internal milieu, the intestinal epithelium constitutes the first structural component facing potential luminal threats to homeostasis. This single-cell layer is the epicenter of a tightly regulated communication network between external and internal factors that converge to prime defensive responses aimed at limiting antigen penetration and the maintenance of intestinal barrier function. The defensive role developed by intestinal epithelial cells (IEC) relies largely on the variety of receptors they express at both extracellular (apical and basolateral) and intracellular compartments, and the capacity of IEC to communicate with immune and nervous systems. IEC recognize pathogen-associated molecules by innate receptors that promote the production of mucus, antimicrobial substances, and immune mediators. Epithelial cells are key to oral tolerance maintenance and also participate in adaptive immunity through the expression of immunoglobulin (Ig) receptors and by promoting local Ig class switch recombination. In IEC, different types of antigens can be sensed by multiple immune receptors that share signaling pathways to assure effective responses. Regulated defensive activity maintains intestinal homeostasis, whereas a breakdown in the control of epithelial immunity can increase the intestinal passage of luminal content and microbial invasion, leading to inflammation and tissue damage. In this review, we provide an updated overview of the type of immune receptors present in the human intestinal epithelium and the responses generated to promote effective barrier function and maintain mucosal homeostasis.

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Glutamine Protects Intestinal Barrier Function of Colon Epithelial Cells from Ethanol by Modulating Hsp70 Expression

Pharmacology ◽

10.1159/000345930 ◽

2013 ◽

Vol 91 (1-2) ◽

pp. 104-111 ◽

Cited By ~ 13

Author(s):

Reiko Akagi ◽

Michiko Ohno ◽

Kiminori Matsubara ◽

Mitsuaki Fujimoto ◽

Akira Nakai ◽

...

Keyword(s):

Epithelial Cells ◽

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Hsp70 Expression

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A Soybean Resistant Protein-Containing Diet Increased the Production of Reg3γ Through the Regulation of the Gut Microbiota and Enhanced the Intestinal Barrier Function in Mice

Frontiers in Nutrition ◽

10.3389/fnut.2021.701466 ◽

2021 ◽

Vol 8 ◽

Author(s):

Tasuku Ogita ◽

Fu Namai ◽

Ayane Mikami ◽

Takahiro Ishiguro ◽

Koji Umezawa ◽

...

Keyword(s):

Epithelial Cells ◽

Barrier Function ◽

Functional Food ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Bacterial Invasion ◽

Direct Stimulation ◽

Intestinal Homeostasis ◽

Food Component ◽

Freeze Dried

The maintenance of intestinal homeostasis is necessary for a good quality of life, and strengthening of the intestinal barrier function is thus an important issue. Therefore, we focused on soybean resistant protein (SRP) derived from kori-tofu (freeze-dried tofu), which is a traditional Japanese food, as a functional food component. In this study, to investigate the effect of SRP on the intestinal barrier function and intestinal microbiota, we conducted an SRP free intake experiment in mice. Results showed that ingestion of SRP decreased the serum level of lipopolysaccharide-binding protein and induced the expression of Reg3γ, thereby improving the intestinal barrier function. In addition, SRP intake induced changes in the cecal microbiota, as observed by changes in β-diversity. In particular, in the microbiota, the up-regulation of functional gene pathways related to the bacterial invasion of epithelial cells (ko05100) was observed, suggesting that Reg3γ expression was induced by the direct stimulation of epithelial cells. The results of this study suggest that SRP is a functional food component that may contribute to the maintenance of intestinal homeostasis.

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The Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Axis in Intestinal Epithelial Cells Regulates Intestinal Barrier Function During Intestinal Epithelial Cells–CD4+T-Cell Interactions

Cellular Physiology and Biochemistry ◽

10.1159/000491985 ◽

2018 ◽

Vol 48 (3) ◽

pp. 1188-1200 ◽

Cited By ~ 8

Author(s):

Tanzhou Chen ◽

Ruoyang Lin ◽

Sisi Jin ◽

Renpin Chen ◽

Haibo Xue ◽

...

Keyword(s):

T Cell ◽

Epithelial Cells ◽

Barrier Function ◽

Intestinal Barrier ◽

Cd4 T Cell ◽

Intestinal Barrier Function ◽

T Cell Proliferation ◽

Intestinal Epithelial ◽

Mhc Ii ◽

Sphingosine 1 Phosphate

Background/Aims: Epithelial cells line the intestinal mucosa and form an important barrier for maintaining host health. This study aimed to explore the mechanism of the Sphingosine-1-phosphate (S1P)/Sphingosine-1-phosphate receptor 2 (S1PR2) pathway in intestinal epithelial cells (IECs) that participate in the intestinal barrier function. Methods: In this study, we constructed a knockout of the S1PR2 gene in mice, and Dextra sulfate sodium (DSS) was used to induce colitis. We isolated IECs from wild type (WT) and S1PR2–/– mice, and the endogenous expression of S1PR2 and Zonula occludens 1 (ZO-1) in IEC were detected by Western blot. Next, the major histocompatibility complex II (MHC-II) expression was analyzed by reverse transcription quantitative real-time (RT-qPCR) and flow cytometry. The in vivo and in vitro intestinal permeability were evaluated by serum fluorescein isothiocyanate (FITC) concentration. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) levels in cell suspension were analyzed by enzyme-linked immuno sorbent assay (ELISA). A carboxyfluorescein diacetate succinimidyl ester (CFSE) assay was used to detect the T-cell proliferation in a co-culture system. Results: The intestinal mucosal barrier damage in S1PR2–/– mice was more severe than in the WT mice, and there were more CD4+T-cells in the colon tissue of DSS-treated S1PR2–/– mice. Either the mouse colon carcinoma cell line (CT26. WT) or the IECs upregulated MHC-II expression, which then promoted CD4+T-cell proliferation. The S1P/S1PR2 pathway controlled MHC-II expression to regulate CD4+T-cell proliferation via the extracellular signal-regulated kinase (ERK) pathway. In addition, the IFN-γ that was secreted by CD4+T-cells increased DSS-induced damage of intestinal epithelial cell barrier function. ZO-1 expression was increased by S1P in CT26.WT cells, while S1PR2 antagonist JTE-013 expression was downregulated. However, in CT26.WTsi-S1PR2 cells, S1P had no effect on ZO-1 expression. Conclusions: The S1P/S1PR2 axis in IECs mediated CD4+T-cell activation via the ERK pathway and MHC-II expression to regulate intestinal barrier function.

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