SEARCH · Search PubMed

Results for “Intestinal barrier”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources

PubMed1991

[Structural bases of the barrier-protective function of the stomach and small intestine].

The gastrointestinal tract acts as a barrier-protective tool in addition to its digestive and transport functions. The structural bases of the barrier protective function of the stomach and small intestine were shown in health, duodenal ulcer (DU), experimental gastroduodenal ulcers (GDU), vagotomy, and peritonitis in case of the interaction of these structures with parietal microflora (PM) which may be a valid criteria for assessing the barrier-protective function. PM increases in number in DU, GDU, vagotomy, and peritonitis. Various modifying interventions can normalize this parameter. Identifying the components of protective levels makes it possible to differentiate the affect of protective levels and makes it possible to differentiate affect some links of the barrier-protective function in order to restore it or prevent its disturbance.

Animals↗

PubMed2005

Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2.

Toll-like receptors (TLR) and NOD2 are emerging as key mediators of innate host defence in the intestinal mucosa, crucially involved in maintaining mucosal as well as commensal homeostasis. Recent observations suggest new (patho-) physiological mechanisms of how functional versus dysfunctional TLRx/NOD2 pathways may oppose or favour inflammatory bowel disease (IBD). In health, TLRx signalling protects the intestinal epithelial barrier and confers commensal tolerance whereas NOD2 signalling exerts antimicrobial activity and prevents pathogenic invasion. In disease, aberrant TLRx and/or NOD2 signalling may stimulate diverse inflammatory responses leading to acute and chronic intestinal inflammation with many different clinical phenotypes.

Bacteria↗

PubMed2006

Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease.

The intestinal epithelial barrier is frequently disrupted in inflammatory bowel disease (IBD) and this has been proposed to play a role in disease pathogenesis and reactivation. In vitro studies show that cytokine-induced epithelial barrier dysfunction can be mediated by increased myosin light chain kinase (MLCK) expression and subsequent myosin II regulatory light chain (MLC) phosphorylation. However, this has never been examined in human disease. The aim of these studies, therefore, was to determine whether MLCK is upregulated in the intestinal epithelium of IBD patients. MLCK expression and MLC phosphorylation in human intestinal resection and biopsy specimens were determined by quantitative immunofluorescence microscopy and correlated with clinical and histopathological data. The data show that ileal epithelial MLCK expression was mildly upregulated in inactive IBD. Expression increased further in active disease, with progressive increases in MLCK expression correlating positively with histological disease activity. This correlation between activity and MLCK expression was also seen in individual patients where areas of differing disease activity were analyzed. Colonic epithelial MLCK expression was similarly increased in active IBD and these increases also correlated positively with disease activity, both in individual patients and the overall study group. To evaluate MLCK enzymatic activity, MLC phosphorylation was assessed in snap-frozen colon biopsies. MLC phosphorylation was significantly increased in biopsies with active, but not inactive, IBD. Therefore, these data show that MLCK expression and enzymatic activity are increased in IBD. Moreover, the correlation with disease activity suggests that MLCK upregulation may contribute to barrier dysfunction and IBD pathogenesis.

Adult↗

PubMed1982

Ultrastructure of gut-associated lymphoid tissue (GALT) in the amphibian urodele, Pleurodeles waltlii.

The ultrastructure of gut-associated lymphoid tissue (GALT) has been studied in the salamander, Pleurodeles waltlii. Lymphoid accumulations appear as true infiltrates scattered throughout the lamina propria cell elements. The most important components of these infiltrates are small and medium sized lymphocytes, and, in lesser amounts, developing and mature plasma cells, macrophages and granulocytes. Migrating lymphoid cells massively invade the intestinal epithelium inducing noticeable modifications, such as the disappearance of the basement membrane and decreased numbers of mucous cells. Thus, in its organization and cell composition, the GALT of P. waltlii appears to represent a primitive phylogenetic precursor of the mammalian "intestinal-immunologic" barrier.

Animals↗

PubMed1988

Intestinal transport of some macromolecules in food.

This review focuses on the intestinal transport of macromolecules in food. Although it is known that neonates have the ability to absorb proteins from the intestine as a means of passive immunization, it has generally been assumed that adults do not retain this capability. A number of studies have shown that the adult mammalian small intestine is capable of transporting a variety of macromolecules in food to a very limited extent. The evidence demonstrating the transport of test substances in the micron-size range across the adult intestinal epithelial barrier is examined for a number of food substances and environmental contaminants. It will be shown that macromolecules can be transported across this barrier by endocytosis; by uptake into the gut-associated lymphoid tissue, and possibly by uptake into the goblet cells. It is considered highly unlikely that large micron-sized particles pass between intestinal cells due to the integrity of the tight junctions between cells that exclude particles in this size range. Quantitative estimates for macromolecular uptake are included along with a discussion of the physiological parameters influencing macromolecular transport.

Animals↗

PubMed2004

Review article: the aetiopathogenesis of inflammatory bowel disease--immunology and repair mechanisms.

Although the aetiopathogenesis of Crohn's disease and ulcerative colitis, remains unsolved, current evidence indicates that defective T-cell apoptosis and impairment of intestinal epithelial barrier function play important roles in the pathogenesis of both conditions. Without appropriate control of T-cell proliferation and death during an immune response, an inappropriate accumulation of T cells and subsequent intestinal inflammation may occur. Differences in T-cell responses between Crohn's disease and ulcerative colitis have been identified, with mucosal T-cell apoptosis being defective in Crohn's disease, but not in ulcerative colitis. Furthermore, cell cycling is considerably faster, with a vigorous clonal expansion, in Crohn's disease, whereas, in ulcerative colitis, T cells cycle normally, but have a remarkably reduced capacity to divide and expand. The elimination of excessive T cells therefore seems to be a reasonable approach to restore the gut to a physiological state or, at least, a controlled state of inflammation. The tumour necrosis factor-alpha blocker, infliximab, exerts its beneficial effects, at least in part, by the induction of apoptosis in lamina propria T cells and monocytes. In addition, repeated damage and injury of the intestinal surface is a hallmark of inflammatory bowel disease and may facilitate the entry of luminal antigens into the mammalian organism and the initiation and perpetuation of both nonspecific and specific immune responses. A better understanding of and enhancement of intestinal repair mechanisms may thus provide future approaches for the treatment of inflammatory bowel disease.

Gastrointestinal Tract↗

PubMed2006

Selective induction of mucin-3 by hypoxia in intestinal epithelia.

Epithelial cells line mucosal surfaces (e.g., lung, intestine) and critically function as a semipermeable barrier to the outside world. Mucosal organs are highly vascular with extensive metabolic demands, and for this reason, are particularly susceptible to diminished blood flow and resultant tissue hypoxia. Here, we pursue the hypothesis that intestinal barrier function is regulated in a protective manner by hypoxia responsive genes. We demonstrate by PCR confirmation of microarray data and by avidin blotting of immunoprecipitated human Mucin 3 (MUC3), that surface MUC3 expression is induced in T84 intestinal epithelial cells following exposure to hypoxia. MUC3 RNA is minimally detectable while surface protein expression is absent under baseline normoxic conditions. There is a robust induction in both the mRNA (first evident by 8 h) and protein expression, first observed and maximally expressed following 24 h hypoxia. This is followed by a subsequent decline in protein expression, which remains well above baseline at 48 h of hypoxia. Further, we demonstrate that this induction of MUC3 protein is associated with a transient increase in the barrier restorative peptide, intestinal trefoil factor (ITF). ITF not only colocalizes with MUC3, by confocal microscopy, to the apical surface of T84 cells following exposure to hypoxia, but is also found, by co-immunoprecipitation, to be physically associated with MUC3, following 24 h of hypoxia. In exploration of the mechanism of hypoxic regulation of mucin 3 expression, we demonstrated by luciferase assay that the full-length promoter for mouse Mucin 3 (Muc3) is hypoxia-responsive with a 5.08 +/- 1.76-fold induction following 24 h of hypoxia. Furthermore, analysis of both the human (MUC3A) and mouse (Muc3) promoters revealed potential HIF-1 binding sites which were shown by chromatin immunoprecipitation to bind the pivotal hypoxia-regulating transcription factor HIF-1alpha. Taken together, these studies implicate the HIF-1alpha mediated hypoxic induced expression of mucin 3 and associated ITF in the maintenance of intestinal barrier function under hypoxic conditions.

Base Sequence↗

PubMed1997

Gut decontamination reduces bowel ischemia-induced lung injury in rats.

OBJECTIVE: To evaluate the effects of gut decontamination on endotoxin, tumor necrosis factor (TNF) levels, and the associated lung injury in a rat model of bowel ischemia. SUMMARY BACKGROUND DATA: Gut ischemia induces disruption of the intestinal mucosal barrier, allowing translocation of bacteria and endotoxin into the blood, which may trigger a systemic inflammatory response and lung injury. METHODS: Thirty anesthetized rats were randomized into three groups: (1) ischemia-reperfusion (I/R) alone (a 60-min superior mesenteric artery occlusion and 4 h of reperfusion, n=10); (2) rats that underwent gut decontamination prior to ischemia (I/R+GD, n=10); and (3) control rats (sham operated, n=10). Serum levels of lipopolysaccharide (LPS) and TNF were measured at the end of the experiment. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. RESULTS: One hour of bowel ischemia and 4 h of reperfusion (I/R) led to elevations of blood LPS and TNF levels of 0.33+/-0.005 EU/mL and 173+/-56 pg/mL, which were higher than the sham group (p<0.01). Gut decontamination (I/R+GD) significantly attenuated the LPS and TNF generation, 0.09+/-0.005 and 56.2+/-6 pg/mL (p<0.01). Lung injury as assessed by pulmonary permeability index was also reduced by gut decontamination, 2.1+/-0.42 vs 5.3+/-0.82 in the control group (p<0.03). Surprisingly no difference was detected in the number of pulmonary neutrophils in sequestration between the groups. CONCLUSIONS: Our data suggest that gut decontamination can reduce the generation of LPS, TNF, and the severity of lung damage that often follows ischemia and reperfusion of the intestine in rats.

Animals↗

PubMed2026

UHRF1 deficiency exacerbates intestinal inflammation by epigenetic modulation of NPY1R gene methylation.

Epigenetic modifications play a crucial role in the pathogenesis of inflammatory bowel disease (IBD) by mediating gene-environment interactions. We previously showed that UHRF1, a central regulator of DNA methylation, contributes to cancer progression; however, its function in IBD remains poorly understood. Here, we revealed that UHRF1 was frequently reduced in inflamed tissues of patients with IBD and that its deficiency exacerbated intestinal epithelial cell (IEC) damage. Through a multilevel approach incorporating human cell models and an intestinal epithelial-specific Uhrf1-KO mouse model, we established UHRF1 as a key mitigator of IBD progression. Mechanistically, UHRF1 bound to the NPY1R promoter, promoted its methylation, and led to transcriptional suppression. The NPY1R upregulation resulting from UHRF1 deficiency attenuated cAMP/PKA/CREB signaling in IECs, thereby enhancing NF-κB activation and subsequent proinflammatory responses, which compromised intestinal epithelial barrier integrity. Furthermore, we identified miR-141 as a negative regulator of NPY1R, highlighting its potential as a therapeutic agent. Collectively, our results identified the UHRF1/NPY1R regulatory axis as a critical epigenetic mechanism in intestinal inflammation and underscored its dual promise for IBD diagnostics and therapy.

Animals↗

PubMed2005

Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion.

The functional integrity of the intestinal epithelial barrier forms a major defense against invading pathogens, including gastrointestinal-dwelling nematodes, which are ubiquitous in their distribution worldwide. Here, we show that an increase in the rate of epithelial cell turnover in the large intestine acts like an "epithelial escalator" to expel Trichuris and that the rate of epithelial cell movement is under immune control by the cytokine interleukin-13 and the chemokine CXCL10. This host protective mechanism against intestinal pathogens has implications for our wider understanding of the multifunctional role played by intestinal epithelium in mucosal defense.

Animals↗

PubMed1984

Intestinal permeability to polyethyleneglycol 600 in relation to macromolecular 'closure' in the neonatal pig.

The intestinal permeability of different sized molecules in the neonatal pig was investigated. Piglets of varying age (0-168 h) were given a mixture of different sized polyethyleneglycols (414-942 dalton polyethyleneglycols) together with ovalbumin and bovine serum albumin by stomach tube, and the serum concentrations were determined two hours after feeding. Considerable amounts of ovalbumin and bovine serum albumin were found in the serum of animals up to 24 hours of age, whereas very little or none at all was found in sera from older animals. By contrast, an intestinal permeability barrier to polyethyleneglycols in the 414-942 dalton range was found not only in the older animals but in all pigs investigated, including the newborn, unsuckled. In addition, the permeability barrier to polyethyleneglycols was found in a pig which was starved to prevent macromolecular closure and, therefore, absorbed considerable amounts of bovine serum albumin and ovalbumin. These findings indicate that 414-942 dalton polyethyleneglycols cross the intestinal mucosa at different rates due to size regardless of age of the animals and regardless of whether the mucosa is permeable to protein or not. This suggests that low molecular weight molecules like 414-942 dalton polyethyleneglycols and macromolecules (proteins) cross the neonatal gut wall through different routes.

Animals↗

PubMed1992

Bacterial translocation from the gastrointestinal tract.

Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal tract to extraintestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. The major mechanisms promoting bacterial translocation in animal models are: (a) disruption of the ecologic equilibrium to allow intestinal bacterial overgrowth, (b) deficiencies in host immune defenses, and (c) increased permeability of the intestinal mucosal barrier. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. Studies are presented of attempts to delineate the mechanisms promoting bacterial translocation utilizing animal models of intestinal bacterial overgrowth, immunosuppression, T-cell deficiencies, solid tumors, leukemia, diabetes, endotoxemia, hemorrhagic shock, thermal injury, bowel obstruction, bile duct ligation, protein malnutrition and parenteral nutrition. Also described are the use of selective antibiotic decontamination or nonspecific macrophage immunomodulators in attempts to reduce bacterial translocation from the gastrointestinal tract.

Animals↗

PubMed1989

Hypoperfusion of the intestinal microcirculation without decreased cardiac output during live Escherichia coli sepsis in rats.

In order to determine the intestinal microvascular responses to normotensive, high cardiac output (CO) bacteremia, we measured vascular diameters and blood flow at different levels of the intestinal microcirculation during live E. coli bacteremia in male Sprague-Dawley rats (n = 16). Precollicular brainstem transection was used to allow study free of drug anesthesia. The microcirculation of a loop of small intestine (with intact neurovascular connections) was observed by in vivo video microscopy and optical Doppler velocimetry at a magnification of x1,500. Intraluminal microvessel diameters and red cell velocity were measured in successive branches until the vessel entered a villus. CO was measured by transpulmonary thermodilution. Intravenous infusion of 1 x 10(9) live E. coli caused a 20% increase in CO at 50 min and a 14% decrease in systemic vascular resistance. However, microvascular blood flow to the small intestine decreased by 27% at 1 hr and by 56% at 2 hr. Progressive arteriolar constriction (25-50%, P less than .05) occurred at all levels of the intestinal microcirculation. These data indicate that intestinal hypoperfusion caused by arteriolar constriction occurs during high CO bacteremia. This hypoperfusion could contribute to mucosal injury and intestinal mucosal barrier dysfunction during sepsis.

Animals↗

PubMed2000

Entamoeba histolytica cysteine proteinases with interleukin-1 beta converting enzyme (ICE) activity cause intestinal inflammation and tissue damage in amoebiasis.

The protozoan parasite Entamoeba histolytica causes intestinal inflammation and ulceration. Amoebic trophozoites activate the transcription factor NF-kappa B in human intestinal epithelial cells, initiating an inflammatory response programme with resultant damage to the intestinal tissue. Amoebic cysteine proteinases have been proposed as important virulence factors for amoebiasis. To test the role of amoebic cysteine proteinases in the pathogenesis of amoebic colitis, human intestinal xenografts in SCID mice were infected with E. histolytica trophozoites expressing an antisense message to ehcp5. The cysteine proteinase-deficient amoeba failed to induce intestinal epithelial cell production of the inflammatory cytokines interleukin (IL)-1B and IL-8, and caused significantly less gut inflammation and damage to the intestinal permeability barrier. The critical role of amoebic cysteine proteinases in human gut inflammation and tissue damage may be explained by our discovery that amoebic cysteine proteinases possess IL-1B converting enzyme (ICE) activity. This ICE activity could contribute to intestinal inflammation by activating human pIL-1B released by damaged intestinal cells. These results demonstrate for the first time that amoebic cysteine proteinases are a key virulence factor in amoebic colitis, and provide a novel mechanism for their activity.

Amebiasis↗

PubMed2004

Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice.

BACKGROUND & AIMS: Effective therapeutics for treating acute colitis, caused by disruption of the intestinal epithelial barrier, are scarce. Trefoil factors (TFF) are cytoprotective and promote epithelial wound healing and reconstitution of the gastrointestinal tract, which makes them good candidate therapeutics for acute colitis. However, orally administered TFF stick to the mucus of the small intestine and are absorbed at the cecum. METHODS: We have engineered the food-grade bacterium Lactococcus lactis to secrete bioactive murine TFF. The protective and therapeutic potentials of these TFF-secreting L. lactis were evaluated in parallel with purified TFF in the dextran sodium sulfate (DSS)-induced murine model for acute colitis and in established chronic colitis in interleukin (IL)-10(-/-) mice. Disease was evaluated by blinded macroscopic and microscopic inflammatory scores and by myeloperoxidase activity. RESULTS: Intragastric administration of TFF-secreting L. lactis led to active delivery of TFF at the mucosa of the colon and, in contrast to administration of purified TFF, proved to be very effective in prevention and healing of acute DSS-induced colitis. The in situ secreted murine TFF significantly decreased morbidity and mortality and stimulated prostaglandin-endoperoxide synthase 2 expression, which represents a major therapeutic pathway. In addition, this approach was successful in improving established chronic colitis in IL-10(-/-) mice. CONCLUSIONS: We have positively evaluated a new therapeutic approach for acute and chronic colitis that involves in situ secretion of murine TFF by orally administered L. lactis. This novel approach may lead to effective management of acute and chronic colitis and epithelial damage in humans.

Acute Disease↗

PubMed1998

Intestinal trefoil factor induces inactivation of extracellular signal-regulated protein kinase in intestinal epithelial cells.

Intestinal trefoil factor (ITF), a small, compact protease-resistant peptide, is abundantly expressed in goblet cells of large and small intestine. Although several biological activities of ITF have been identified, including promotion of wound healing, stimulation of epithelial cell migration, and protection of intestinal epithelial barrier, little is known about signaling events through which ITF mediates its physiological function. In this study, the effects of exogenous ITF on mitogen-activated protein kinase (MAPK) signaling cascades were examined in IEC-6 cells, a nontransformed intestinal epithelial cell line that does not express endogenous trefoil peptides. Stimulation with ITF resulted in rapid decrease in extracellular signal-related protein kinase (ERK) activity and concomitant reduced ERK tyrosine phosphorylation. ITF also decreased activation of ERK activity induced by either transforming growth factor-alpha, which links extracellular stimuli to the Ras/Raf/MEK/ERK pathway via the epidermal growth factor receptor, or phorbol 12-myristate 13-acetate, which activates Raf through protein kinase C. ITF-induced inhibition of ERK activity was blocked by an inhibitor of tyrosine and dual-specific phosphatases, sodium orthovanadate. In summary, ITF leads to inhibition of ERK and the MAPK pathway through activation of tyrosine or dual-specific phosphatase.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1985

Aging-associated increase in intestinal absorption of macromolecules.

The intestinal permeability of aging rats to various molecular weight species of polyethylene glycol 400 (PEG 400) was studied. Animals received a bolus of PEG 400 by oral gavage and urine was collected for 6 h to assess its rate of absorption. Quantitation by gas liquid chromatography revealed that total urinary excretion of PEG 400 increased with aging. 34-week-old rats excreted 34.3% of the administrated dose while 43.6% was excreted in the urine by rats 133 weeks of age. This effect was more pronounced with the higher molecular weight PEG since excretion of the lower molecular weight PEG 282 decreased by 10.5% while PEG 634 excretion increased by 11.4% with aging. The increased permeability of the intestinal tract to higher molecular weight species of PEG may indicate that the intestinal protective barrier to the absorption of potentially harmful environmental substances may be less efficient in aging animals. If similar findings are found in aging humans, they may indicate increased potential for absorption of large antigenic or carcinogenic compounds from the intestinal lumen.

Aging↗

PubMed1998

Serosal but not mucosal endotoxin exposure increases intestinal permeability in vitro in the rat.

BACKGROUND: Microbial endotoxins are normally present in the gut, usually without apparent harmful effects, whereas systemically administered endotoxin impairs the mucosal barrier function. Our aim was to investigate whether in vitro exposure to bacterial lipopolysaccharide (LPS) could affect the intestinal barrier properties of the rat small intestine. METHODS: Small-intestinal segments from rats were mounted in Ussing diffusion chambers, and the mucosal to serosal permeation of the marker molecules bovine serum albumin (BSA) and 51Cr-ethylenediaminetetraacetic acid (EDTA) was measured after addition of LPS to the mucosal or serosal side. RESULTS: Mucosal exposure to LPS (0.01, 0.05, 0.25 mg/ml) had no effects on the permeation of BSA and 51Cr-EDTA, whereas when added to the serosal side at 0.05 or 0.25 mg/ml, LPS increased the marker permeation. CONCLUSION: Serosal LPS exposure in vitro increased the intestinal permeability to the different-sized markers, whereas mucosal LPS did not, indicating that the mechanisms leading to intestinal barrier impairment can be initiated in the intestinal wall itself.

Animals↗