scholarly journals 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

2018 ◽  
Vol 48 (3) ◽  
pp. 1188-1200 ◽  
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.

scholarly journals PTPN2 Regulates Interactions Between Macrophages and Intestinal Epithelial Cells to Promote Intestinal Barrier Function

2020 ◽  
Vol 159 (5) ◽  
pp. 1763-1777.e14 ◽  
Author(s):  
Marianne R. Spalinger ◽  
Anica Sayoc-Becerra ◽  
Alina N. Santos ◽  
Ali Shawki ◽  
Vinicius Canale ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial

scholarly journals Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danyang Zheng ◽  
Henan Zhou ◽  
Hongchen Wang ◽  
Yu Zhu ◽  
Yue Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Dynamic Balance ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Mitochondrial Dynamic ◽  
Intestinal Barrier Dysfunction

Abstract Background Sepsis is a major cause of death in ICU, and intestinal barrier dysfunction is its important complication, while the treatment is limited. Recently, mesenchymal stem cell-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment; whether MMVs are therapeutic in sepsis induced-intestinal barrier dysfunction is obscure. Methods In this study, cecal ligation and puncture-induced sepsis rats and lipopolysaccharide-stimulated intestinal epithelial cells to investigate the effect of MMVs on intestinal barrier dysfunction. MMVs were harvested from mesenchymal stem cells and were injected into sepsis rats, and the intestinal barrier function was measured. Afterward, MMVs were incubated with intestinal epithelial cells, and the effect of MMVs on mitochondrial dynamic balance was measured. Then the expression of mfn1, mfn2, OPA1, and PGC-1α in MMVs were measured by western blot. By upregulation and downregulation of mfn2 and PGC-1α, the role of MMVs in mitochondrial dynamic balance was investigated. Finally, the role of MMV-carried mitochondria in mitochondrial dynamic balance was investigated. Results MMVs restored the intestinal barrier function by improving mitochondrial dynamic balance and metabolism of mitochondria. Further study revealed that MMVs delivered mfn2 and PGC-1α to intestinal epithelial cells, and promoted mitochondrial fusion and biogenesis, thereby improving mitochondrial dynamic balance. Furthermore, MMVs delivered functional mitochondria to intestinal epithelial cells and enhanced energy metabolism directly. Conclusion MMVs can deliver mfn2, PGC-1α, and functional mitochondria to intestinal epithelial cells, synergistically improve mitochondrial dynamic balance of target cells after sepsis, and restore the mitochondrial function and intestinal barrier function. The study illustrated that MMVs might be a promising strategy for the treatment of sepsis.

scholarly journals Epithelial PBLD attenuates intestinal inflammatory response and improves intestinal barrier function by inhibiting NF-κB signaling

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Shengbo Chen ◽  
Hongbin Liu ◽  
Zhijun Li ◽  
Jingyi Tang ◽  
Bing Huang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Trinitrobenzene Sulfonic Acid ◽  
Intestinal Epithelial ◽  
Colonic Tissue ◽  
Tnf Α

AbstractIntestinal barrier function defects and dysregulation of intestinal immune responses are two key contributory factors in the pathogenesis of ulcerative colitis (UC). Phenazine biosynthesis-like domain-containing protein (PBLD) was recently identified as a tumor suppressor in gastric cancer, hepatocellular carcinoma, and breast cancer; however, its role in UC remains unclear. Therefore, we analyzed colonic tissue samples from patients with UC and constructed specific intestinal epithelial PBLD-deficient (PBLDIEC−/−) mice to investigate the role of this protein in UC pathogenesis. We found that epithelial PBLD was decreased in patients with UC and was correlated with levels of tight junction (TJ) and inflammatory proteins. PBLDIEC−/− mice were more susceptible to dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid-induced colitis compared with wild-type (WT) mice. In DSS-induced colitis, PBLDIEC−/− mice had impaired intestinal barrier function and greater immune cell infiltration in colonic tissue than WT mice. Furthermore, TJ proteins were markedly reduced in PBLDIEC−/− mice compared with WT mice with colitis. Nuclear factor (NF)-κB activation was markedly elevated and resulted in higher expression levels of downstream effectors (C–C motif chemokine ligand 20, interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) in colonic epithelial cells isolated from PBLDIEC−/− mice than WT mice with colitis. PBLD overexpression in intestinal epithelial cells (IECs) consistently inhibited TNF-α/interferon-γ-induced intestinal barrier disruption and TNF-α-induced inflammatory responses via the suppression of NF-κB. In addition, IKK inhibition (IKK-16) rescued excessive inflammatory responses induced by TNF-α in PBLD knockdown FHC cells. Co-immunoprecipitation assays showed that PBLD may interact with IKKα and IKKβ, thus inhibiting NF-κB signaling, decreasing inflammatory mediator production, attenuating colonic inflammation, and improving intestinal barrier function. Modulating PBLD expression may provide a novel approach for treatment in patients with UC.

Abstract 645: Curcumin Modulates the Function(s) of Intestinal Epithelial Cells: Role in the Development of Diet-Induced Metabolic Diseases

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jing Wang ◽  
Siddhartha S Ghosh ◽  
Shobha Ghosh
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Metabolic Diseases ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Oral Supplementation ◽  
Pre Treatment ◽  
Induced Changes

Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from high fat high cholesterol containing western type diet (WD)-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. We demonstrated earlier that WD-induced changes in intestinal barrier function increases the release of LPS into systemic circulation and oral supplementation with curcumin not only reduces the levels of systemic LPS but also attenuates the subsequent development of glucose intolerance and atherosclerosis. Although curcumin is reported to exert potent anti-inflammatory effects in vitro , its poor bioavailability has raised doubts about a causal relationship between oral supplementation and the in vivo effects. It is hypothesized that curcumin attenuates WD-induced chronic inflammation and associated metabolic diseases by modulating the function of intestinal epithelial cells (IECs) and the objective of the present study was to delineate the underlying mechanisms. Human IEC lines, Caco-2, HT-29 and T-84 were used for these studies and modulation of direct as well as indirect effects of LPS on tight junctions as well as intracellular signaling were examined. Pre-treatment with Curcumin prevented LPS-induced disruption of tight junctions. LPS-induced secretion of master cytokine IL-1β was also dramatically reduced by pre-treatment with curcumin. Furthermore, curcumin also attenuated IL-1β induced activation of p-38 MAPK involved in the phosphorylation of tight junction proteins and subsequent disruption of their normal arrangement. Based on these data, the sites of curcumin actions leading to preservation of intestinal barrier function are shown in the Figure (activation and inhibition denoted by + and - symbols in green circles).

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

scholarly journals Arctigenin fromFructus Arctii(Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Hee Soon Shin ◽  
Sun Young Jung ◽  
Su Yeon Back ◽  
Jeong-Ryong Do ◽  
Dong-Hwa Shon
Keyword(s):  
Barrier Function ◽  
Active Component ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Traditional Herbal Medicine ◽  
Cell Monolayers ◽  
Basolateral Side

Fructus Arctiiis used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect ofF. Arctiiextract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component ofF. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment ofF. Arctiiincreased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component ofF. Arctiiincreased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed thatF. Arctiicould enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin fromF. Arctiicould contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function.

scholarly journals Plumericin Protects against Experimental Inflammatory Bowel Disease by Restoring Intestinal Barrier Function and Reducing Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Barrier Function ◽  
Structural Integrity ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.

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