Gastrointestinal dysfunction induced by early weaning is attenuated by delayed weaning and mast cell blockade in pigs

2007 ◽  
Vol 293 (2) ◽  
pp. G413-G421 ◽  
Author(s):  
Adam J. Moeser ◽  
Kathleen A. Ryan ◽  
Prashant K. Nighot ◽  
Anthony T. Blikslager
Keyword(s):  
Mast Cell ◽  
Intestinal Mucosa ◽  
Barrier Function ◽  
Electrical Resistance ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Mast Cell Activation ◽  
Mucosal Barrier ◽  
Early Weaning ◽  
Mucosal Barrier Function

Our previous work has demonstrated that weaning at 19 days of age has deleterious effects on mucosal barrier function in piglet intestine that are mediated through peripheral CRF receptor signaling pathways. The objectives of the present study were to assess the impact of piglet age on weaning-associated intestinal dysfunction and to determine the role that mast cells play in weaning-induced breakdown of mucosal barrier function. Nursing Yorkshire-cross piglets were either weaned at 19 days of age (early-weaned, n = 8) or 28 days of age (late-weaned, n = 8) and housed in nursery pens. Twenty-four hours postweaning, segments of midjejunum and ascending colon from piglets within each weaning age group were harvested and mounted on Ussing chambers for measurements of transepithelial electrical resistance and serosal-to-mucosal [3H]mannitol fluxes. Early weaning resulted in reductions in transepithelial electrical resistance and increases in mucosal permeability to [3H]mannitol in the jejunum and colon ( P < 0.01). In contrast, postweaning reductions in intestinal barrier function were not observed in piglets weaned at 28 days of age. Early-weaned piglet intestinal mucosa had increased expression of CRF receptor 1 protein, increased mucosal mast cell tryptase levels, and evidence of enhanced mast cell degranulation compared with late-weaned intestinal mucosa. Pretreatment of piglets with the mast cell stabilizer drug cromolyn, injected intraperitoneally 30 min prior to weaning, abolished the early-weaning-induced intestinal barrier disturbances. Our results indicate that early-weaning stress induces mucosal dysfunction mediated by intestinal mast cell activation and can be prevented by delaying weaning.

scholarly journals Intestinal Mucosal Barrier Function Restoration in Mice by Maize Diet Containing Enriched Flavan-4-Ols

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 896 ◽  
Author(s):  
Binning Wu ◽  
Rohil Bhatnagar ◽  
Vijaya V. Indukuri ◽  
Shara Chopra ◽  
Kylie March ◽  
...  
Keyword(s):  
Barrier Function ◽  
Control Diet ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Low Grade ◽  
Colonic Inflammation ◽  
Mucosal Barrier Function ◽  
Inflammatory Bowel ◽  
Histology Score

Inflammatory bowel disease (IBD), a chronic intestinal inflammatory condition, awaits safe and effective preventive strategies. Naturally occurring flavonoid compounds are promising therapeutic candidates against IBD due to their great antioxidant potential and ability to reduce inflammation and improve immune signaling mediators in the gut. In this study, we utilized two maize near-isogenic lines flavan-4-ols-containing P1-rr (F+) and flavan-4-ols-lacking p1-ww (F−) to investigate the anti-inflammatory property of flavan-4-ols against carboxymethylcellulose (CMC)-induced low-grade colonic inflammation. C57BL/6 mice were exposed to either 1% CMC (w/v) or water for a total of 15 weeks. After week six, mice on CMC treatment were divided into four groups. One group continued on the control diet. The second and third groups were supplemented with F+ at 15% or 25% (w/w). The fourth group received diet supplemented with F− at 15%. Here we report that mice consuming F+(15) and F+(25) alleviated CMC-induced increase in epididymal fat-pad, colon histology score, pro-inflammatory cytokine interleukin 6 expression and intestinal permeability compared to mice fed with control diet and F−(15). F+(15) and F+(25) significantly enhanced mucus thickness in CMC exposed mice (p < 0.05). These data collectively demonstrated the protective effect of flavan-4-ol against colonic inflammation by restoring intestinal barrier function and provide a rationale to breed for flavan-4-ols enriched cultivars for better dietary benefits.

scholarly journals Macrophage Deficiency Makes Intestinal Epithelial Cells Susceptible to NSAID-Induced Damage

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xinxin Wang ◽  
Jiayang Wang ◽  
Tianyu Xie ◽  
Shuo Li ◽  
Di Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Epithelial Proliferation ◽  
Gm Csf ◽  
Mucosal Barrier Function

Objectives. In Crohn’s disease (CD), the mechanisms underlying the regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of mucosal barrier function in the ileum are unclear. We analyzed the molecular mechanisms underlying the regulation by GM-CSF of the mucosal barrier function. Methods. We examined the role of GM-CSF in the intestinal barrier function in CD at the molecular-, cellular-, and animal-model levels. Results. Macrophages directly secreted GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis, which maintained intestinal barrier function. Macrophages were absent in NSAID-induced ileitis, causing GM-CSF deficiency, increasing the apoptosis rate, decreasing the proliferation rate, increasing inter- and paracellular permeabilities, decreasing the TJP levels, and reducing the numbers of mesenteric lymph nodes, memory T cells, and regulatory T cells in Csf1op/op transgenic mice. Conclusions. GM-CSF is required for the maintenance of intestinal barrier function. Macrophages directly secrete GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis.

scholarly journals Carbon Monoxide Releasing Molecule-2 Protects Intestinal Mucosal Barrier Function of Rat Undergoing Cardiopulmonary Resuscitation via Attenuation of TNF-α/NF-κB Signaling

2021 ◽  
Author(s):  
Qingsheng Niu ◽  
Fang Liu ◽  
Jun Zhang ◽  
Xiaojun Yang ◽  
Xiaohong Wang
Keyword(s):  
Carbon Monoxide ◽  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Intestinal Mucosa ◽  
Barrier Function ◽  
Mucosal Barrier ◽  
Intestinal Mucosal Barrier ◽  
Expression Levels ◽  
Tnf Α ◽  
Mucosal Barrier Function

Abstract The unique features of post–cardiac arrest pathophysiology are often superimposed on the disease or injury, causing the cardiac arrest, as well as underlying comorbidities. Exogenous carbon monoxide (CO) was reported to reduce ischemia-reperfusion injury (IRI). This study aimed to assess the effects of CO releasing molecule-2 (CORM-2) on intestinal mucosal barrier function after cardiopulmonary resuscitation (CPR) in rats. For this purpose, we established a rat model of asphyxiation-induced cardiac arrest and resuscitation to study intestinal IRI, and measured the serum level of intestinal fatty-acid binding protein (I-FABP). The expression levels of claudin-3, occludin, ZO-1, tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and nuclear factor kappa B (NF-κB) p65 were detected by Western blotting. CORM-2 up-regulated the expression levels of tight junction proteins (claudin-3, occludin, and ZO-1) in intestinal mucosa, leading to the reduction of the permeability of intestinal mucosa and reduced the release of proinflammatory cytokines. Besides, the CORM-2 exhibited anti-inflammatory effects by regulating the TNF-α/NF-κB pathway. In conclusion, CORM-2 treatment is clinically significant, preventing intestinal mucosal damage as a result of IRI during CPR.

scholarly journals PO-105 Exercise regulates HMGB1 / TLR4 / NF- κ B pathway by H2S to improve OJ intestinal injury

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Changfeng Shao ◽  
Jiaqin Chen ◽  
Wei Chen ◽  
Qi Peng ◽  
Di Li ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Obstructive Jaundice ◽  
Aerobic Exercise ◽  
Intestinal Mucosa ◽  
Barrier Function ◽  
Immunohistochemical Staining ◽  
Mucosal Barrier ◽  
Intestinal Mucosal Barrier ◽  
Qrt Pcr ◽  
Mucosal Barrier Function

Objective To study the effect of aerobic exercise on the damage of intestinal mucosal barrier function caused by obstructive jaundice（OJ）and to explore its mechanism of action. Methods  50 male KM mice were randomly divided into 5 groups: sham operation group (S), model group (M), exercise group (TM), DL-Propargylglycine + exercise (PT) group and sodium hydrosulfide + exercise (NT) group.In addition to the S group which are in the common bile duct to the abdominal wall hanging 48 hours to build mouse obstructive jaundice model. In the PT group, PAG (40 mg/kg) was intraperitoneally injected 7 days after surgery; NaHS (50 μmol/kg) was intraperitoneally injected in the NT group 7 days after surgery; TM group, NT group and PT group were graded at 0%, and the speed was 10m/min no weight training (30min/day).After 6 weeks, HE staining was used to observe the morphological changes of the intestinal mucosa.Biochemical analysis was used to detect the concentration of hydrogen sulfide (H2S) in blood and ileum, and total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) Liver function, diamine oxidase (DAO), D-lactic acid intestinal barrier function biochemical index; qRT-PCR and immunohistochemical staining were used to observe the expression changes of H2S-mediated related channel mRNA and protein（HMGB1, TLR4 and NF-Kbp6）in intestinal tissues. Results HE staining showed that the intestinal mucosa of group M was atrophied and the villus was broken.Compared with M group, the intestinal mucosa arrangement in TM group was relatively regular. Compared with TM group, intestinal mucosa atrophy in PT group, fluff hair loss, sparseness and disorder, partial mucosa The layer was separated from the lamina propria and the gland was severely damaged. The intestinal mucosa of the NT group was relatively regular, and the changes of intestinal mucosa atrophy were restored. Serum test results showed that H2S levels were higher in the TM group than in the M group; compared with the TM group, the PT group decreased and the NT group increased. DAO level: The TM group was lower than the M group; compared with the TM group, the PT group was elevated and the NT group was decreased.  Changes in serum D-lactic acid levels were similar to DAO. The results of qRT-PCR and immunohistochemical staining showed that the expressions of HMGB1, TLR4 and NF-Kbp6 mRNA and protein in the intestinal tissues of mice in TM group were significantly lower than those in M group and PT group, and the mRNA and protein expression levels in NT group were the lowest. Conclusions Aerobic exercise inhibits the HMGB1 / TLR4 / NF-κB signaling pathway through the H2S / CSE system, thereby exerting a protective effect on the intestinal mucosal barrier.

scholarly journals Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 135 ◽  
Author(s):  
Mercé Albert-Bayo ◽  
Irene Paracuellos ◽  
Ana M. González-Castro ◽  
Amanda Rodríguez-Urrutia ◽  
María J. Rodríguez-Lagunas ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Cell Activity ◽  
Intestinal Barrier ◽  
The Body ◽  
Mast Cell Activation ◽  
Mucosal Barrier ◽  
Mucosal Mast Cell

The gastrointestinal tract harbours the largest population of mast cells in the body; this highly specialised leukocyte cell type is able to adapt its phenotype and function to the microenvironment in which it resides. Mast cells react to external and internal stimuli thanks to the variety of receptors they express, and carry out effector and regulatory tasks by means of the mediators of different natures they produce. Mast cells are fundamental elements of the intestinal barrier as they regulate epithelial function and integrity, modulate both innate and adaptive mucosal immunity, and maintain neuro-immune interactions, which are key to functioning of the gut. Disruption of the intestinal barrier is associated with increased passage of luminal antigens into the mucosa, which further facilitates mucosal mast cell activation, inflammatory responses, and altered mast cell–enteric nerve interaction. Despite intensive research showing gut dysfunction to be associated with increased intestinal permeability and mucosal mast cell activation, the specific mechanisms linking mast cell activity with altered intestinal barrier in human disease remain unclear. This review describes the role played by mast cells in control of the intestinal mucosal barrier and their contribution to digestive diseases.

scholarly journals 124 Butyric acid and derivatives: In vitro effects on barrier integrity of porcine intestinal epithelial cells quantified by transepithelial electrical resistance

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 109-110
Author(s):  
Lauren L Kovanda ◽  
Monika Hejna ◽  
Yanhong Liu
Keyword(s):  
Butyric Acid ◽  
Sodium Butyrate ◽  
Barrier Function ◽  
Electrical Resistance ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial

Abstract Intestinal barrier function in vitro is quantified by the transepithelial electrical resistance (TEER) across epithelial cell monolayers due to polarization and expression of tight junction proteins. The objective of the current study was to measure the TEER of porcine intestinal epithelial cells (IPEC-J2) treated with butyric acid, sodium butyrate, monobutyrin and tributyrin. MTT assays were performed for each compound to determine cell viability and appropriate treatment doses. Butyric acid and tributyrin treatments were: 0, 0.5, 1, 2, and 4 mM. Monobutyrin and sodium butyrate doses were: 0, 1, 2, 4, 8 mM. Cells were seeded at 5 × 105 cells/mL into 12-well plates on Corning transwell inserts. Cells were cultured for 4 to 5 days (until all wells had TEER close to 1000 Ωcm2) and were then treated with organic acids. Each compound was tested in a randomized complete block design with 10 replicates. TEER was measured in Ωcm2 using a Millicell ERS-2 voltohmmeter at 0 h (before treatment) and at 24, 48, and 72 h post-treatment. All data were analyzed by PROC MIXED of SAS. Butyric acid linearly enhanced (P &lt; 0.001) TEER of IPEC-J2 dose-dependently, with the highest TEER observed at doses of 1 and 2 mM at each time point. Sodium butyrate did not impact TEER at h 24, but linearly increased (P &lt; 0.05) TEER at h 48 and 72. Treatment of monobutyrin linearly improved (P &lt; 0.001) TEER at h 24, 48, and 72, with the highest TEER observed at the dose of 8 mM. Tributyrin had the tendency to improve (P &lt; 0.10) TEER at h 48 and 72 when the highest dose was applied. Results of the current in vitro study indicate that butyric acid and its derivatives may improve intestinal barrier function of pigs, which requires verification in vivo.

scholarly journals Early weaning stress impairs development of mucosal barrier function in the porcine intestine

2010 ◽  
Vol 298 (3) ◽  
pp. G352-G363 ◽  
Author(s):  
Feli Smith ◽  
Jessica E. Clark ◽  
Beth L. Overman ◽  
Christena C. Tozel ◽  
Jennifer H. Huang ◽  
...  
Keyword(s):  
Mast Cells ◽  
Barrier Function ◽  
Life Stress ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Mucosal Barrier ◽  
Early Weaning ◽  
Barrier Dysfunction ◽  
Weaned Pigs ◽  
Mucosal Barrier Function

Early life stress is a predisposing factor for the development of chronic intestinal disorders in adult life. Here, we show that stress associated with early weaning in pigs leads to impaired mucosal barrier function. Early weaning (15- to 21-day weaning age) resulted in sustained impairment in intestinal barrier function, as indicated by reductions in jejunal transepithelial electrical resistance and elevations in mucosal-to-serosal flux of paracellular probes [3H]mannitol and [14C]inulin measured at 5 and 9 wk of age, compared with that shown in late-weaned pigs (23- to 28-day weaning age). Elevated baseline short-circuit current was observed in jejunum from early-weaned pigs and was shown to be mediated via enhanced Cl− secretion. Jejunal barrier dysfunction in early-weaned pigs coincided with increased lamina propria immune cell density particularly mucosal mast cells. The mast cell stabilizer drug sodium cromoglycolate ameliorated barrier dysfunction and hypersecretion in early-weaned pigs, demonstrating an important role of mast cells. Furthermore, activation of mast cells ex vivo with c48/80 and corticotrophin-releasing factor (CRF) in pig jejunum mounted in Ussing chambers induced barrier dysfunction and elevations in short-circuit current that were inhibited with mast cell protease inhibitors. Experiments in which selective CRF receptor antagonists were administered to early-weaned pigs revealed that CRF receptor 1 (CRFr1) activation mediates barrier dysfunction and hypersecretion, whereas CRFr2 activation may be responsible for novel protective properties in the porcine intestine in response to early life stress.

scholarly journals Asparagine preserves intestinal barrier function from LPS-induced injury and regulates CRF/CRFR signaling pathway

2017 ◽  
Vol 23 (6) ◽  
pp. 546-556 ◽  
Author(s):  
Huiling Zhu ◽  
Dingan Pi ◽  
Weibo Leng ◽  
Xiuying Wang ◽  
Chien-An Andy Hu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Signaling Pathway ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Villous Atrophy ◽  
Intestinal Barrier ◽  
Intestinal Morphology ◽  
Mast Cell Activation ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction

Stress causes intestinal inflammation and barrier dysfunction. Corticotrophin-releasing factor (CRF)/CRF receptor (CRFR) signaling pathway has been shown to be important for stress-induced intestinal mucosal alteration. L-Asparagine (ASN) is a powerful stimulator of ornithine decarboxylase and cell proliferation in a variety of cell types, including colonic cells. In the present study, we investigated whether dietary ASN supplementation could alleviate the damage of intestinal barrier function caused by LPS through modulation of CRF/CRFR signaling pathway. Twenty-four weaned pigs were randomly divided into one of four treatments: (1) non-challenged control; (2) Escherichia coli LPS challenged control; (3) LPS + 0.5% ASN; (4) LPS + 1.0% ASN. LPS stress induced villous atrophy, intestinal morphology disruption and decreased claudin-1 expression. ASN supplementation increased intestinal claudin-1 protein expression and alleviated villous atrophy and intestinal morphology impairment caused by LPS stress. In addition, ASN supplementation increased the number of intestinal intraepithelial lymphocytes and reversed the elevations of intestinal mast cell number and neutrophil number induced by LPS stress. Moreover, ASN decreased the mRNA expression of intestinal CRF, glucocorticoid receptors and tryptase. These results indicate that ASN attenuates intestinal barrier dysfunction induced by LPS stress, and regulates CRF/CRFR1 signaling pathway and mast cell activation.

scholarly journals Chitosan Ameliorates DSS-Induced Ulcerative Colitis Mice by Enhancing Intestinal Barrier Function and Improving Microflora

2019 ◽  
Vol 20 (22) ◽  
pp. 5751 ◽  
Author(s):  
Jia Wang ◽  
Cuili Zhang ◽  
Chunmei Guo ◽  
Xinli Li
Keyword(s):  
Barrier Function ◽  
Intestinal Microflora ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Tight Junction Proteins ◽  
Intestinal Mucosal Barrier ◽  
Tnf Α ◽  
Mucosal Barrier Function ◽  
Junction Proteins

Ulcerative colitis (UC) has been identified as one of the inflammatory diseases. Intestinal mucosal barrier function and microflora play major roles in UC. Modified-chitosan products have been consumed as effective and safe drugs to treat UC. The present work aimed to investigate the effect of chitosan (CS) on intestinal microflora and intestinal barrier function in dextran sulfate sodium (DSS)-induced UC mice and to explore the underlying mechanisms. KM (Kunming) mice received water/CS (250, 150 mg/kg) for 5 days, and then received 3% DSS for 5 days to induce UC. Subsequently, CS (250, 150 mg/kg) was administered daily for 5 days. Clinical signs, body weight, colon length, and histological changes were recorded. Alterations of intestinal microflora were analyzed by PCR-DGGE, expressions of TNF-α and tight junction proteins were detected by Western blotting. CS showed a significant effect against UC by the increased body weight and colon length, decreased DAI (disease activity index) and histological injury scores, and alleviated histopathological changes. CS reduced the expression of TNF-α, promoted the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1 to maintain the intestinal mucosal barrier function for attenuating UC in mice. Furthermore, Parabacteroides, Blautia, Lactobacillus, and Prevotella were dominant organisms in the intestinal tract. Blautia and Lactobacillus decreased with DSS treatment, but increased obviously with CS treatment. This is the first time that the effect of original CS against UC in mice has been reported and it is through promoting dominant intestinal microflora such as Blautia, mitigating intestinal microflora dysbiosis, and regulating the expressions of TNF-α, claudin-1, occludin, and ZO-1. CS can be developed as an effective food and health care product for the prevention and treatment of UC.

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