scholarly journals Role of the Kaiso gene in the development of inflammation in Mucin-2 defcient mice

2019 ◽  
Vol 22 (8) ◽  
pp. 1078-1083
Author(s):  
E. A. Litvinova ◽  
K. M. Achasova ◽  
M. A. Borisova ◽  
S. V. Zhenilo ◽  
E. B. Prokhortchouk ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Experimental Model ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gene Encoding ◽  
Mucin 2 ◽  
Mucin Layer

The number of people with inflammatory bowel disease (IBD) is constantly increasing worldwide. The main factors that have effects on the etiology of the disease are genetic, environmental and immunological. However, the mechanism of disease development and effective treatment of IBD have not yet been found. Animal models help address these problems. The most popular model is considered to be transgenic models in which individual genes are knocked out. One of such models for the study of IBD are mice with a null mutation of theMuc2gene encoding the Mucin-2 protein, which is involved in the formation of a protective mucin layer in the small and large intestine. Some of transcription factors that change the expression of intestinal genes are involved in the development of IBD and colorectal cancer. One of such transcription factors is “zinc fnger” domain-containing protein Kaiso which is able to bind to methylated DNA. In this study, we assessed the role of Kaiso in the development of intestinal inflammation using the experimental model of C57BL/6Muc2-/-Kaiso-/-. We have shown that mice with impaired intestinal barrier function that develop processes similar to human IBD also develop inflammatory responses, such as increased expression ofIl1,TnfandIl17agenes. The defciency of the Kaiso transcription factor in Mucin-2 knockout mice causes a decrease in the expression level of only theCox2andTff3genes. Perhaps a decline in the expression of the gene encoding cyclooxygenase-2 can lead to a decrease in the expression of the antibacterial factor Trefoil factor 3. However, in the experimental model of IBD, Kaiso protein did not play a signifcant role in the regulation of pro-inflammatory cytokines of tumor necrosis factor and interleukins 1 and 17.

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 The Role of Gut Microbiota in Intestinal Inflammation with Respect to Diet and Extrinsic Stressors

2019 ◽  
Vol 7 (8) ◽  
pp. 271 ◽  
Author(s):  
Stefani Lobionda ◽  
Panida Sittipo ◽  
Hyog Young Kwon ◽  
Yun Kyung Lee
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Environmental Stressors ◽  
Intestinal Barrier Function ◽  
Symbiotic Relationship ◽  
Inflammatory Bowel ◽  
Host Metabolism ◽  
The Relationship

The gut microbiota maintains a symbiotic relationship with the host and regulates several important functions including host metabolism, immunity, and intestinal barrier function. Intestinal inflammation and inflammatory bowel disease (IBD) are commonly associated with dysbiosis of the gut microbiota. Alterations in the gut microbiota and associated changes in metabolites as well as disruptions in the intestinal barrier are evidence of the relationship between the gut microbiota and intestinal inflammation. Recent studies have found that many factors may alter the gut microbiota, with the effects of diet being commonly-studied. Extrinsic stressors, including environmental stressors, antibiotic exposure, sleep disturbance, physical activity, and psychological stress, may also play important roles in altering the composition of the gut microbiota. Herein, we discuss the roles of the gut microbiota in intestinal inflammation in relation to diet and other extrinsic stressors.

A role for Campylobacter jejuni-induced enteritis in inflammatory bowel disease?

2010 ◽  
Vol 298 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Lisa D. Kalischuk ◽  
Andre G. Buret
Keyword(s):  
Campylobacter Jejuni ◽  
Intestinal Microflora ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
New Therapeutic Approaches ◽  
Bowel Diseases ◽  
Host Genetic ◽  
Inflammatory Bowel

The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are T cell-mediated diseases that are characterized by chronic, relapsing inflammation of the intestinal tract. The pathogenesis of IBD involves the complex interaction between the intestinal microflora, host genetic and immune factors, and environmental stimuli. Epidemiological analyses have implicated acute bacterial enteritis as one of the factors that may incite or exacerbate IBD in susceptible individuals. In this review, we examine how interactions between the common enteric pathogen Campylobacter jejuni ( C. jejuni ), the host intestinal epithelium, and resident intestinal microflora may contribute to the pathogenesis of IBD. Recent experimental evidence indicates that C. jejuni may permit the translocation of normal, noninvasive microflora via novel processes that implicate epithelial lipid rafts. This breach in intestinal barrier function may, in turn, prime the intestine for chronic inflammatory responses in susceptible individuals. Insights into the interactions between enteric pathogens, the host epithelia, and intestinal microflora will improve our understanding of disease processes that may initiate and/or exacerbate intestinal inflammation in patients with IBD and provide impetus for the development of new therapeutic approaches for the treatment of IBD.

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 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 The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 959 ◽  
Author(s):  
Jefferson Antônio Leite ◽  
Gabriela Pessenda ◽  
Isabel C. Guerra-Gomes ◽  
Alynne Karen Mendonça de Santana ◽  
Camila André Pereira ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Bacterial Translocation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Dna Sensor ◽  
Proinflammatory Response

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.

scholarly journals EnteroaggregativeEscherichia coliAdherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Erik J. Boll ◽  
Jorge Ayala-Lujan ◽  
Rose L. Szabady ◽  
Christopher Louissaint ◽  
Rachel Z. Smith ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Cell Receptor ◽  
Host Cell Receptor ◽  
Intestinal Infections ◽  
Elevated Expression ◽  
Intestinal Pathogen ◽  
Proinflammatory Role ◽  
First Time

ABSTRACTEnteroaggregativeEscherichia coli(EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen.IMPORTANCEEAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs—the principal adhesins of EAEC—in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.

scholarly journals The Role of Intestinal Barrier Function in Early Life in the Development of Colitis

Colitis ◽  
10.5772/25753 ◽  
2012 ◽  
Author(s):  
R.C. Anderson ◽  
J.E. Dalziel ◽  
P.K. Gopal ◽  
S. Bassett ◽  
A. Ellis ◽  
...  
Keyword(s):  
Barrier Function ◽  
Early Life ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function

scholarly journals Intestinal Barrier Function and Performance of Broiler Chickens Fed Additional Arginine, Combination of Arginine and Glutamine or an Amino Acid-Based Solution

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2416
Author(s):  
Reza Barekatain ◽  
Tristan Chalvon-Demersay ◽  
Clive McLaughlan ◽  
William Lambert
Keyword(s):  
Amino Acid ◽  
Intestinal Permeability ◽  
Broiler Chickens ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Basal Diet ◽  
Intestinal Barrier Function ◽  
Glutathione Synthetase ◽  
Feed Conversion ◽  
Experimental Treatments

Two experiments were conducted to investigate the effect of arginine (Arg); the combination of Arg and glutamine (Gln); as well as an amino acid-based solution (MIX) containing Arg, Gln, threonine (Thr), and grape extract, on performance, intestinal permeability, and expression of selected mechanistic genes. Using 240 male Ross 308 off-sex broiler chickens, four experimental treatments were replicated six times with 10 birds per replicate. The experimental treatments included 5 g/kg Arg, 2.5 g/kg Arg and 2.5 g/kg Gln, and 1 g/kg MIX added to a basal diet as control. In the second study, the four dietary treatments were then given to 24 birds with or without a synthetic glucocorticoid, dexamethasone (DEX), as a gut dysfunction model. Feed conversion ratio was improved by all the supplemented treatments from day 7 to 35 of age (p < 0.001). DEX injections increased (p < 0.001) the intestinal permeability in all treatments, which tended to be reversed by Arg or MIX. Additional Arg, Arg-Gln, and MIX suppressed (p < 0.05) the overexpression of IL-1β generated by DEX. Feeding birds with MIX treatment increased (p < 0.05) expression of SGLT-1 and glutathione synthetase. In conclusion, tested amino acid supplements were effective in improving feed efficiency and restraining intestinal inflammation caused by DEX through IL-1β pathway.

scholarly journals Anthocyanins and intestinal barrier function: a review

2019 ◽  
Vol 5 ◽  
pp. 18-30 ◽  
Author(s):  
Jonathan C. Valdez ◽  
Bradley W. Bolling
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Berry Anthocyanins ◽  
Chronic Intestinal Inflammation

Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation. Berries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and preventing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocyanins and their known microbial catabolites modulate intestinal barrier function.

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