SEARCH · PubMed Health

Results for “Intestinal Barrier Function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 1,027 records · Page 57Linked to original sources

PubMed1980

Crohn's disease: transmission electron microscopic studies. I. Barrier function. Possible changes related to alterations of cell coat, mucous coat, epithelial cells, and Paneth cells.

Surgically resected specimens and grossly normal resection margins from patients with Crohn's disease and normal controls were studied by a variety of ultrastructural techniques. This work describes changes in three anatomic barriers--mucus, cell coat, and epithelial cells--found in this disease. As seen by transmission electron microscopy, mucus was increased in diseased areas as well as in the margins of resection. The thickness of the cell coat was moderately increased in resection margins but not in diseased areas. Detachment and losses of cell coat were noted in some diseased areas. A marked increase in cytoplasmic dense vesicles suggests increased losses and increased production of cell coat in diseased areas. Goblet cells and epithelial cells showed no consistent signs of cell injury. Epithelial cells in diseased areas had markedly shortened microvilli and an increase in lysosomes. Paneth cells were increased in number and showed both focal granule extrusion and cytoplasmic lysosomal inclusions. The possible significance of these findings in terms of barrier function and uptake phenomena is discussed.

Crohn Disease↗

PubMed1976

Maturation of intestinal defenses against peroral infection with group B coxsackievirus in mice.

The intestinal tract of adult mice provides effective protection against peroral infection with group B coxsackievirus. This protective function consists of at least two separate components. One is a barrier effect that prevents virus from passing through the mucosal side of the gut into the circulation. It becomes clearly evident at 18 days of life and is present thereafter. The other is a clearance mechanism that acts to eliminate virus from the enteric tract after infection has occurred. This is first demonstrable at about 14 to 18 days and also persists. The appearance of these protective functions coincides with the known development of enzymatic and morphological changes in the gut associated with the transition from suckling to weanling.

Administration, Oral↗

PubMedDate not supplied

Host responses to Cryptosporidium infection.

Cryptosporidium is a clinically and economically important infection whose pathogenic effect begins with colonization of the intestinal epithelium. Despite intensive efforts, a consistently effective therapy for the infection has yet to be identified. Morbidity and mortality results from ongoing loss of absorptive epithelium, which leads to villous atrophy and malabsorption and release of inflammatory mediators that stimulate electrolyte secretion and diarrhea. With further clarification of the mechanisms underlying enterocyte malfunction in Cryptosporidium infection, it should be possible to design rational nutritional and pharmacologic therapies to enhance nutrient and water absorption, promote the clearance of infected enterocytes, and restore normal villus architecture and mucosal barrier function.

Animals↗

PubMed2003

TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells.

BACKGROUND & AIMS: NOD2, a member of the NOD1/Apaf-1 family, was recently identified as the first susceptibility gene for Crohn's disease. The aim of this report was to describe the regulation and functional significance of NOD2 expression in intestinal epithelial cells. METHODS: Expression of NOD2 messenger RNA was determined by reverse-transcription polymerase chain reaction (RT-PCR); NOD2 protein was detected by Western blot. Promoter activity was assessed by reporter gene assays and DNA-binding of NF-kappaB by electrophoretic mobility shift assays. IL-8 production was investigated by RT-PCR and enzyme-linked immunosorbent assay. RESULTS: TNF-alpha induced an up-regulation of NOD2 in epithelial cell lines (HT-29, SW620, SW948, HeLa S3) and in primary colonic epithelial cells. A synergism was seen by cotreatment with IFN-gamma. Two NF-kappaB binding sites were identified in the promoter. Deletion of either site or overexpression of dominant negative IkappaBalpha led to reduced levels of TNF-alpha/IFN-gamma-stimulated reporter gene activity. The identified kappaB3 site was bound by NF-kappaB as determined by gelshift assays. Elevated amounts of NOD2 protein were also found in colonic epithelial cells from patients with IBD. LPS induced high levels of IL-8 production in SW620 cells overexpressing NOD2. CONCLUSIONS: TNF-alpha(/IFN-gamma) treatment up-regulates the expression of the NOD2 gene in intestinal epithelial cells and subsequently increases their LPS susceptibility. Together with the mutation-derived truncation and functional change of the NOD2 protein, this could be part of the complex pathophysiology of barrier disruption as it is observed in inflammatory bowel diseases.

Antineoplastic Agents↗

PubMed2005

Bifidobacterium breve and Streptococcus thermophilus secretion products enhance T helper 1 immune response and intestinal barrier in mice.

Lactic acid bacteria or their secretion products can modulate immune responses differently in normal and inflammatory conditions. This comparative study analyzes the effect of oral administration of living lactic acid bacteria, or their conditioned media, on the epithelial and immune functions of colitis-prone C57BL/6 IL-10-deficient mice. Mice were untreated (control) or infected with Helicobacter hepaticus with or without oral treatment with living bacteria, Bifidobacterium breve C50 and Streptococcus thermophilus 065 (LB), or their culture-conditioned media (CM). Histology, cytokine mRNA, electrical resistance, and barrier capacity of colonic samples as well as cytokine secretion by mesenteric lymph node (MLN) cells were studied. Helicobacter hepaticus mice developed only mild colitis, which was not modified in LB or CM groups. In the CM (but not the LB) group, the colonic barrier was reinforced as compared to the other groups, as evidenced by decreased horseradish peroxidase (HRP) transcytosis and mannitol fluxes and increased electrical resistance. In MLN, the percentage of CD4+ and CD8+ T cells secreting IFNgamma was significantly higher in CM (2.06% and 1.98%, respectively) mice than in H. hepaticus (1.1% and 0.47%, P < 0.05) or control mice. In addition, the nonspecific stimulation of IFNgamma, TNFalpha, and IL-12 secretion by MLN cells was significantly higher in the CM group as compared to the other groups. In the absence of severe colitis, Bifidobacterium breve C50- and Streptococcus thermophilus 065-conditioned media can reinforce intestinal barrier capacity and stimulate Th1 immune response, highlighting the involvement of lactic acid bacteria-derived components in host defense.

Animals↗

PubMed1989

[Pathology of the digestive organs and systemic endotoxinemia].

The intestine being a natural depot of the gram-negative bacteria, may be the source of the systemic endotoxinemia in various pathologic processes followed by the increase of bacteria death, mucous membrane damage, pancreas endocrine function deficiency, liver barrier function depression, decrease of the portal circulation speed or its shunting. At the same time, the systemic endotoxinemia in itself may be one of the most important etiological factors of the various digestive organs injury. The authors observations and the literature suggest an important role of the endotoxin-positive granulocytes in the pathogenesis of the haemorrhagic infarct of the intestine, mesenteric vein thrombosis, destructive appendicitis and cholecystitis.

Digestive System Diseases↗

PubMed1992

Immunologic structure and function of the gastrointestinal tract.

Host defenses within the gastrointestinal tract exclude bacteria and other intraluminal substances, which if released into the systemic circulation, would be toxic to the body. This is accomplished via complex interactions between these external pathogens and local immune responses and nonimmunologic processes. In addition to the mechanical and chemical barriers of the nonimmunologic defense system within the gastrointestinal tract, there is an effective immunologic barrier composed of aggregated and nonaggregated lymphoid cells. Gut-associated lymphoid tissue protects the intestinal mucosa from invading pathogens by intricate pathways of antigen processing. Gut-associated lymphoid tissue also transfers protection to other secretory sites within the body through the common mucosal immune system. The integrity of both the immunologic and nonimmunologic barriers may be affected by any number of pathologic insults as well as by nutritional influences. This article reviews the structural and functional characteristics of this complex and critically important host defense system. Specific nutrient requirements of the immunologic processes are discussed.

Critical Illness↗

PubMed2004

Pseudoallergic reactions in chronic urticaria are associated with altered gastroduodenal permeability.

BACKGROUND: In a subgroup of patients with chronic urticaria (CU) the disease is caused by pseudoallergic reactions to food. The aim of this study was to investigate whether disturbances of the gastrointestinal barrier function play a role in the pathomechanism of the disease. METHODS: In 55 patients with CU gastrointestinal permeability was measured with an in vivo triple-sugar-test before and after 24 days of a diet low in pseudoallergens. Sucrose served as marker for gastroduodenal permeability, lactulose/mannitol ratio for intestinal permeability. RESULTS: Basal gastroduodenal and intestinal permeability were significantly higher in patients with urticaria as compared to controls. In 29 of the 55 patients skin symptoms decreased or completely disappeared during the diet (responders). Compared to nonresponders (n = 26), responders had a significantly higher gastroduodenal permeability before treatment (0.36 +/- 0.04 vs 0.15 +/- 0.01% sucrose; P < 0.001), which decreased after the diet (0.17 +/- 0.02; P < 0.001). The number of patients with Helicobacter pylori infections did not differ between the two groups. CONCLUSIONS: The results indicate that in a subgroup of patients with CU and pseudoallergy an impaired gastroduodenal barrier function may be of pathophysiological importance. The underlying mechanisms seem to be independent of H. pylori infection.

Adult↗

PubMed2004

The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract.

Eosinophils and the gastrointestinal tract interact in an intimate and enigmatic relationship. Under healthy conditions, the presence of eosinophils is limited almost exclusively to the digestive tract mucosa where they exert several effector and immunoregulatory functions. While their precise function in the gastrointestinal tract is not completely understood, it is likely that, together with different T cell subsets, eosinophils are involved in maintaining the immunologic homeostastis across the mucosal barrier under resting conditions. Eosinophils also play a role in several inflammatory conditions, such as intestinal infections, hypersensitivity reactions, primary eosinophilic inflammations and several other chronic intestinal disorders. Depending on the responsible trigger, their effects may be beneficial or detrimental. Here, we discuss the available information regarding the physiological and pathological functions of eosinophils within the gastrointestinal tract.

Digestive System↗

PubMed2006

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships.

The solute carrier family 10 (SLC10) comprises two sodium-dependent bile acid transporters, i.e. the Na(+)/taurocholate cotransporting polypeptide (NTCP; SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT; SLC10A2). These carriers are essentially involved in the maintenance of the enterohepatic circulation of bile acids mediating the first step of active bile acid transport through the membrane barriers in the liver (NTCP) and intestine (ASBT). Recently, four new members of the SLC10 family were described and referred to as P3 (SLC10A3), P4 (SLC10A4), P5 (SLC10A5) and sodium-dependent organic anion transporter (SOAT; SLC10A6). Experimental data supporting carrier function of P3, P4, and P5 is currently not available. However, as demonstrated for SOAT, not all members of the SLC10 family are bile acid transporters. SOAT specifically transports steroid sulfates such as oestrone-3-sulfate and dehydroepiandrosterone sulfate in a sodium-dependent manner, and is considered to play an important role for the cellular delivery of these prohormones in testes, placenta, adrenal gland and probably other peripheral tissues. ASBT and SOAT are the most homologous members of the SLC10 family, with high sequence similarity ( approximately 70%) and almost identical gene structures. Phylogenetic analyses of the SLC10 family revealed that ASBT and SOAT genes emerged from a common ancestor gene. Structure-activity relationships of NTCP, ASBT and SOAT are discussed at the amino acid sequence level. Based on the high structural homology between ASBT and SOAT, pharmacological inhibitors of the ASBT, which are currently being tested in clinical trials for cholesterol-lowering therapy, should be evaluated for their cross-reactivity with SOAT.

Amino Acid Sequence↗

PubMed2005

[Protective effects of acidic fibroblast growth factor on intestinal ischemia/reperfusion in rats].

OBJECTIVE: To observe the change in hepatic and renal functions, change in the plasma D-lactate level, and the expression of proliferating cell nuclear antigen (PCNA) after intestinal I/R injury, so as to explore the effects of reconstructive human acid fibroblast growth factor(aFGF) on intestinal I/R injury in rats. METHODS: One hundred and twenty-six Wistar rats were divided into sham-operated, ischemia (45 minutes) plus reperfusion, reconstructive human aFGF treatment (2, 4, 8 microg aFGF) and wild type aFGF(2, 6, 12, and 24 hours, respectively) groups. Hepatic and renal functions and the levels of plasma D-lactate were determined and the expression of PCNA was assessed. RESULTS: Compared with all other groups, bowel barrier function and hepatic and renal functions showed most marked deterioration in sham-operated group. The damages were less marked in reconstructive human aFGF group compared with other groups 24 hours after ischemia/reperfusion of the intestine, and the protective effect was best shown when 4 microg of aFGF was given. The trend of expression of PCNA was similar to that of changes in D-lactate level. CONCLUSION: Wild type reconstructive human aFGF treatment significantly improves the outcome of ischemia/reperfusion injury to the intestine, and the effect is dose-dependent.

Animals↗

PubMed1994

Nutritional support of the gut: how and why.

Trauma, sepsis, and other conditions of stress are characterized by a hypermetabolic state, in which markedly increased substrate availability is required to meet energy demands for tissue repair and host defenses. Inability to meet these increased metabolic demands results in accelerated visceral protein depletion, impaired immune function, and impaired wound healing. In addition, alteration of the gut flora, impaired host immune defenses, or direct gut mucosal injury may result in gut barrier failure. All of the above derangements, acting in concert, may ultimately lead to sepsis or multiple organ failure. Since enteral nutrition improves resistance to experimentally induced infections, blunts the hypermetabolic response to injury, and maintains intestinal structure and function better than parenteral nutrition, there are many reasons to favor a policy of early enteral feeding in critically ill patients. We demonstrated the safety and efficacy of immediate enteral feeding in patients with major thermal injury, and have found this practice to be applicable to a wide variety of other critically ill patients. These patients had not been felt to be candidates for enteral nutrition due to unfounded fears related to the presence of ileus or fresh gastrointestinal anastomosis.

Animals↗

PubMed1996

The immunologic aspects of human immunodeficiency virus infection in the gastrointestinal tract.

The intestinal (in particular rectal) mucosa is an important portal of entry of human immunodeficiency virus (HIV) in homosexual men, who represent the vast majority of HIV-infected patients in Europe and North America. There are several possibilities for HIV to reach the CD4+ T cells, macrophages, and follicular dendritic cells in the intestinal mucosa. HIV may be transported through M cells directly to mucosal lymphoid follicles. Alternatively, HIV may infect enterocytes via Fc-receptor by antibody-bound HIV or via a CD4 independent receptor. By successive budding on the basal side of enterocytes, HIV may be released into the lamina propria. Furthermore, in patients not infected by the intestinal route, HIV may also rapidly enter the intestinal mucosa by other mechanisms: intestinal T-lymphocytes are mainly activated memory T cells reentering the mucosal surfaces after circulating through the peripheral blood. In the periphery they may have been preferentially infected by HIV. Accumulation of infected T cells could thus occur in the intestinal mucosa. The special phenotypical and functional characteristics of intestinal T lymphocytes may affect the replication and cytopathicity of HIV, resulting in an accelerated loss of CD4 positive T cells in the lamina propria. CD4 T cells play a critical role in antigen-dependent B cell differentiation, thus the pronounced CD4 T cell depletion in the intestinal mucosa may be responsible for the observed decrease of IgA plasma cells and a reduced secretion of IgA2. Depletion and functional impairment of activated mucosal lamina propria lymphocytes by HIV infection could explain the break-down of the mucosal immune barrier leading to secondary opportunistic or nonopportunistic infections and secondary malignancies. In addition, because of the interrelation between the mucosal immune system and the epithelium these changes might be responsible for the partial small intestinal mucosal atrophy and maturational defects in enterocytes observed in HIV-infected patients. To be effective, a future prophylactic vaccine against HIV has to be able to induce not only systemic but also a local mucosal cellular and humoral protective immune response.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line.

The MHC class I-related Fc receptor, FcRn, mediates the intestinal absorption of maternal IgG in neonatal rodents and the transplacental transport of maternal IgG in humans by receptor-mediated transcytosis. In mice and rats, expression of FcRn in intestinal epithelial cells is limited to the suckling period. We have recently observed, however, clear expression of FcRn in the adult human intestine, suggesting a function for FcRn in intestinal IgG transport beyond neonatal life in humans. We tested this hypothesis using the polarized human intestinal T84 cell line as a model epithelium. Immunocytochemical data show that FcRn is present in T84 cells in a punctate apical pattern similar to that found in human small intestinal enterocytes. Solute flux studies show that FcRn transports IgG across T84 monolayers by receptor-mediated transcytosis. Transport is bidirectional, specific for FcRn, and dependent upon endosomal acidification. These data define a novel bidirectional mechanism of IgG transport across epithelial barriers that predicts an important effect of FcRn on IgG function in immune surveillance and host defense at mucosal surfaces.

Adult↗

PubMed2006

Intestinal damage in strongyloidiasis: the imbalance between cell death and proliferation.

Strongyloidiasis is an endemic tropical parasitosis caused by Strongyloides stercoralis that also affects immigrants in nontropical countries. The nematode colonizes the duodenum and upper jejunum, inducing mucosal alterations. Because integrity is essential for a functional barrier, we aimed to study apoptosis and proliferation in the small bowel epithelium infected with S. stercoralis. We evaluated 23 patients and 17 controls. Apoptotic cells were detected by TUNEL and M30 immunolabelling, whereas proliferation was scored by Ki67 immunostaining and mitotic counting. Infection increased apoptotic indices in duodenum and jejunum (P < 0.001). Conversely, it decreased cell proliferation in both segments (P < 0.001). Our results showed that intestinal strongyloidiasis promotes an imbalance between cell death and proliferation. This is the first evidence of disruption of the epithelial kinetics with S. stercoralis infection, though the mechanisms remain unclear. Furthermore, our results support the idea that strongyloidiasis disturbs the mucosal integrity and can compromise the intestinal barrier.

Adult↗

PubMed2000

Carbonylation and disassembly of the F-actin cytoskeleton in oxidant induced barrier dysfunction and its prevention by epidermal growth factor and transforming growth factor alpha in a human colonic cell line.

BACKGROUND: Intestinal barrier dysfunction concomitant with high levels of reactive oxygen metabolites (ROM) in the inflamed mucosa have been observed in inflammatory bowel disease (IBD). The cytoskeletal network has been suggested to be involved in the regulation of barrier function. Growth factors (epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha)) protect gastrointestinal barrier integrity against a variety of noxious agents. However, the underlying mechanisms of oxidant induced disruption and growth factor mediated protection remain elusive. AIMS: To determine: (1) if oxidation and disassembly of actin (a key cytoskeletal component) plays a major role in ROM induced epithelial monolayer barrier dysfunction; and (2) if growth factor mediated protection involves prevention of theses alterations. METHODS: Caco-2 monolayers were preincubated with EGF, TGF-alpha, or vehicle before incubation with ROM (H(2)O(2) or HOCl). Effects on cell integrity, barrier function, and G- and F-actin (oxidation, disassembly, and assembly) were determined. RESULTS: ROM dose dependently and significantly increased F- and G-actin oxidation (carbonylation), decreased the stable F-actin fraction (index of stability), and increased the monomeric G-actin fraction (index of disassembly). Concomitant with these changes were disruption of the actin cytoskeleton and loss of the monolayer barrier function. In contrast, growth factor pretreatment decreased actin oxidation and enhanced the stable F-actin, while in concert prevented actin disruption and restored normal barrier function of monolayers exposed to ROM. Cytochalasin-D, an inhibitor of actin assembly, not only caused actin disassembly and barrier dysfunction but also abolished the protective action of growth factors. Moreover, an actin stabilising agent, phalloidin, mimicked the protective actions of the growth factors. CONCLUSIONS: Oxidation, disassembly, and instability of the actin cytoskeleton appears to play a key role in the mechanism of oxidant induced loss of intestinal barrier integrity. In contrast, organisation and stabilisation of actin through promotion of its assembly plays a critical role in the mechanism of growth factor mediated protection.

Actins↗

PubMed1992

Intestinal epithelial restitution. Characterization of a cell culture model and mapping of cytoskeletal elements in migrating cells.

Closure of superficial wounds in epithelia occurs by migration of cells shouldering the wound. We describe an in vitro model of such restitution using a human intestinal epithelial cell line, T84. T84 cells were grown on novel optically transparent type 1 collagen membranes without underlying filter supports. Monolayers so grown display substantial barrier function (400-500 ohm.cm2; 1.3 +/- 0.4 nmol.h-1.cm-2 mannitol flux). Wounds made with micropipettes were accompanied by a fall in resistance and rise in monolayer permeability to mannitol and inulin. After injury, cells shouldering wounds migrated, by extension of lamellipodia-like processes, to reseal wounds as defined by structural and functional criteria. F actin arcs crossed the base of the lamellipodia-like extensions and F actin microspikes projected from the leading edge of these extensions. Villin, an epithelial-specific cytoskeletal protein with both F actin bundling and severing capacities, was also expressed at the leading edge in a pattern consistent with a regulatory role in the dynamic restructuring of lamellipodia. Lastly, myosin II was predominantly localized to the basal regions of lamellipodia, though occasional staining was seen close to the advancing edge. Myosin I, a recently recognized myosin family member considered to be essential for fibroblast and slime mold motility, was present throughout lamellipodia in punctate fashion, but was not concentrated at the leading edge.

Actins↗

PubMed2005

Aetiology of inflammatory bowel disease (IBD): role of intestinal microbiota and gut-associated lymphoid tissue immune response.

The aetiology of inflammatory bowel disease (IBD) probably involves a combination of genetic predisposition and environmental factors that may be channelled through an abnormality in gut-barrier function, with a loss of antigen tolerance. Some genetic markers that predispose to inflammatory disease have been identified (alleles DR2, DRB1*0103, DRB1*12 and mutations in the NOD2/CARD15 gene on chromosome 16). Alterations in the pattern of cytokine production by T cell subclasses leading to loss of tolerance to oral antigens have been documented. Moreover, a number of environmental factors (cigarette smoking, use of non-steroid anti-inflammatory drugs, psychological stress and the presence of the caecal appendix) have been postulated as a trigger of IBD. It has also been suggested that the gut microbiota plays a major role in the development and persistence of IBD, and numerous modifications of intestinal microbiota composition have been identified. As a result, manipulation of the microbiota with antibiotics is a current therapeutic strategy; more recently, however, a number of studies have reported promising results when using probiotic organisms to manipulate gut microbiota composition in order to restore tolerance to microbial antigens of the host's own microbiota.

Animals↗