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.

Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions

2017 ◽  
Vol 8 (3) ◽  
pp. 1144-1151 ◽  
Author(s):  
Qianru Chen ◽  
Oliver Chen ◽  
Isabela M. Martins ◽  
Hu Hou ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Cell Monolayers ◽  
Collagen Peptides ◽  
Epithelial Barrier Dysfunction

Alaska pollock skin derived collagen peptides could be considered as dietary supplements for intestinal barrier function promotion and associated diseases.

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.

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

2011 ◽  
Vol 91 (1) ◽  
pp. 151-175 ◽  
Author(s):  
Alessio Fasano
Keyword(s):  
Gastrointestinal Tract ◽  
Tight Junctions ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
New Paradigm ◽  
Intestinal Epithelial Barrier ◽  
Neoplastic Disorders

The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a “leaky gut” in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

scholarly journals Bridge the Gap – The Efficacy of β-Carotene in Immune Sensing of LPS and Intestinal Barrier Integrity in Colon Epithelial Cells

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 71-71
Author(s):  
Junrui Cheng ◽  
Emilio Balbuena ◽  
Baxter Miller ◽  
Abdulkerim Eroglu
Keyword(s):  
Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Low Grade ◽  
Mrna Levels ◽  
Limited Information ◽  
Barrier Dysfunction ◽  
Barrier Integrity ◽  
Β Carotene

Abstract Objectives Gastrointestinal (GI) disorders are causing significant global health care burden. Lipopolysaccharide (LPS), a structural component of Gram-negative bacteria, induces low-grade inflammation and disturbs GI homeostasis. While the anti-inflammatory function of β-Carotene (BC), a provitamin A carotenoid, has been explored in multiple systems, a limited information exists on the roles of BC in modulating LPS-induced inflammation in colonocytes. Therefore, we aimed to mechanistically investigate the role of BC in LPS-induced colonic inflammation and intestinal barrier dysfunction. Methods Human colon epithelial cells (HT-29) were primed with interferon-γ at 50 ng/mL for 12 hours, then treated with 1 µg/mL LPS and BC at 1, 10, 100 nM, and 1, 10 µM for 15 hours. Inflammatory cytokines were quantified with an ELISA assay. The fold change in mRNA levels was determined by qPCR. Changes in proteins of interest were evaluated using both Western blot and immunocytochemistry (ICC) assays. Results LPS-stimulated production of IL-6 and TNFα levels was inhibited by BC treatment at 10 nM – 1 μM; IL-1β in whole cell lysates and supernatant IL-6 levels were decreased by BC treatment at all dosages. LPS-induced elevation of C-reactive protein and cyclooxygenase-1 mRNA was reversed with 1 μM and 10 μM BC treatment. Claudin-1 and occludin are major tight junction proteins that contribute to maintaining colonic barrier integrity. Intriguingly, BC at 10 nM – 1 μM significantly enhanced claudin-1 and occludin mRNA and protein levels. The up-regulation of claudin-1 was also validated in the ICC assay. A further exploration of the underlying mechanisms showed that BC inhibited the LPS-activated TLR4-NF-κB p65 pathway to alleviate inflammation in the cells. CD14, a membrane protein expressed on the surfaces of epithelial cells, could restore the impaired intestinal barrier function. In this study, an increased CD14 protein level was found in BC-treated cells, which was correlated with the improved claudin-1 and occludin levels, indicating that BC may promote colonic barrier integrity via up-regulating CD14. Conclusions BC plays a role in modulating LPS-induced TLR4 signaling pathway and enhancing gut barrier integrity. These novel findings will shed light on the role of BC in alleviating endotoxin-induced GI disorders. Funding Sources USDA.

II. Stress and intestinal barrier function

2001 ◽  
Vol 280 (1) ◽  
pp. G7-G13 ◽  
Author(s):  
Johan D. Söderholm ◽  
Mary H. Perdue
Keyword(s):  
Barrier Function ◽  
Clinical Course ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Novel Treatments ◽  
Mucosal Barrier Function ◽  
Underlying Mechanisms

The influence of stress on the clinical course of a number of intestinal diseases is increasingly being recognized, but the underlying mechanisms are largely unknown. This themes article focuses on recent findings related to the effects of stress on mucosal barrier function in the small intestine and colon. Experiments using animal models demonstrate that various types of psychological and physical stress induce dysfunction of the intestinal barrier, resulting in enhanced uptake of potentially noxious material (e.g., antigens, toxins, and other proinflammatory molecules) from the gut lumen. Evidence from several studies indicates that in this process, mucosal mast cells play an important role, possibly activated via neurons releasing corticotropin-releasing hormone and/or acetylcholine. Defining the role of specific cells and mediator molecules in stress-induced barrier dysfunction may provide clues to novel treatments for intestinal disorders.

scholarly journals Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

2015 ◽  
Vol 309 (12) ◽  
pp. G988-G997 ◽  
Author(s):  
Prashant Nighot ◽  
Rana Al-Sadi ◽  
Manmeet Rawat ◽  
Shuhong Guo ◽  
D. Martin Watterson ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Protein Expression ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Dss Colitis

Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/−mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/−mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/−mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/−mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/−mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.

scholarly journals BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Protein Levels ◽  
Lps Challenge ◽  
Endotoxemia Model

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

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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