PubMed Health⌕ Search

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 1,207 records · Page 67Linked to original sources
PubMed1997

The Bacteroides fragilis toxin fragilysin disrupts the paracellular barrier of epithelial cells.

Bacteroides fragilis is a member of the normal colonic microflora of most mammals and is the most commonly isolated anaerobe from human clinical specimens. Some strains produce a toxin (fragilysin, a zinc-metalloproteinase) implicated as a cause of diarrheal disease in farm animals and humans. Studies in our laboratory confirm that the proteolytic activity of this toxin is responsible for the fluid secretion and tissue damage observed in vivo. In this study, we investigated the effects of fragilysin on the paracellular barrier of epithelial cells. Researchers suggest that, since the toxin rapidly intoxicates HT-29 cells, it may be internalized. However, we could not prevent cell rounding by using inhibitors of receptor-mediated endocytosis, which indicates that the toxin may act outside the cell. Based on these observations, we studied the effects of the highly purified B. fragilis fragilysin on the barrier function of cultured epithelial cells. Fragilysin rapidly increased the permeability of the paracellular barrier of epithelial cells to ions (decrease in electrical resistance across monolayers) and to larger molecules (increase in mannitol flux across monolayers). We tested a human colon cell line and cell lines from the lung and the kidney; the human colon cell line was most sensitive, but all three were affected in the same manner. Our studies show that B. fragilis fragilysin alters the barrier function of the epithelial lining, possibly by degrading the tight junction proteins, such as ZO-1. The proteolytic activity is required to cause this effect. The toxin's action has been assumed to be limited to the intestine; however, our studies show that fragilysin could also contribute to the pathogenesis of B. fragilis in extraintestinal infections.

Bacterial Toxins↗
PubMedDate not supplied

Regulation of the intestinal glycoprotein glycosylation during postnatal development: role of hormonal and nutritional factors.

This review focuses on the regulation of the glycoprotein glycosylation process in small intestine and colon during postnatal development. Glycoproteins play a prominent part in intestine as mucins secreted by the goblet cells and as molecules of biological interest largely present in the microvillus membrane of the enterocytes (digestive enzymes, transporters). The age-related changes in the intestinal glycosylation control the quality of glycan chains of glycoproteins. Postnatal maturation is observed at all stages of the glycoprotein glycosylation. But it is essentially characterised in the external glycosylation by a shift from sialylation to fucosylation depending on the transcriptional regulation of the corresponding glycosyltransferases, but also on coordinate changes in the activities of glycosyltransferases and of their regulatory proteins, in nucleotide-sugar bioavailability and in product degradation by oxidases. Many factors have been evoked to trigger these changes, among which are hormonal (glucocorticoids, insulin) and dietary factors. Changes in the structure of the glycoprotein glycans might be important for the transport, the barrier function, the implantation of the immune defences and of the microflora and even probably for the biological activity of some digestive enzymes.

Animal Nutritional Physiological Phenomena↗
PubMed2006

The role of caspase-3 in lipopolysaccharide-mediated disruption of intestinal epithelial tight junctions.

The mechanisms responsible for microbially induced epithelial apoptosis and increased intestinal permeability remain unclear. This study assessed whether purified bacterial lipopolysaccharide (LPS) increases epithelial apoptosis and permeability and whether these changes are dependent on caspase-3 activation. In nontumorigenic epithelial monolayers, Escherichia coli O26:B6 LPS increased apoptosis, as shown by nuclear breakdown, caspase-3 activation, and PARP cleavage, and induced disruption of tight junctional ZO-1. Apical, but not basolateral, exposure to LPS increased epithelial permeability. Addition of a caspase-3 inhibitor abolished the effects of LPS. The findings describe a novel mechanism whereby apical LPS may disrupt epithelial tight junctional ZO-1 and barrier function in a caspase-3-dependent fashion.

Apoptosis↗
PubMed1999

Butyrate hastens restoration of barrier function after thermal and detergent injury to rat distal colon in vitro.

BACKGROUND: Epithelial migration restores barrier function after superficial injury to any mucosa. The present study aimed to determine whether butyrate, important to colonic epithelial physiology in diverse ways, influences restoration of barrier function in the injured rat colon. METHODS: Rat distal colon was transiently exposed in vitro to heat (55 degrees C for 10 sec) or to detergent (deoxycholic acid, 7.5 mM, for 15 min), and tissue damage was verified histologically. Epithelial barrier function was assessed, in colon tissue mounted in Ussing chambers, by measuring electric resistance and passive serosa-to-mucosa fluxes of 22Na and of 14C PEG 4000 under voltage clamp conditions. Studies were done in the absence and presence of 25 mM butyrate in the bathing solutions. RESULTS: Heat exposure induced superficial epithelial damage, and the electric resistance decreased significantly. This was accompanied by increase in flux of 14C PEG and increased passive flux of 22Na. Electric resistance was significantly higher, and PEG flux significantly lower, in tissues bathed with butyrate. Exposure to deoxycholic acid also induced superficial epithelial damage, reduced tissue electric resistance, and increased passive flux of Na and PEG. Electric resistance was significantly higher, and PEG flux significantly lower, in injured tissues bathed in butyrate, than in injured tissues bathed in butyrate-free solution. The effect of butyrate on restoration of electric resistance towards normal was seen in colon both from adult rats and from younger rats that were 2 or 6 weeks old. CONCLUSIONS: Butyrate enhanced restoration of mucosal barrier function in rat distal colon in response to heat and detergent injury.

Animals↗
PubMed2005

Mucosal integrity and barrier function in the pathogenesis of early lesions in Crohn's disease.

Crohn's disease aetiology is multifactorial and remains enigmatic. However, animal models show that disease heterogeneity is probable, in that more than one defective mucosal mechanism can produce the same clinical phenotype. For example, Crohn's-like lesions are reported after compromise of mucosal integrity per se in the presence of an intact immune system, through altered expression of mucosal adhesion molecules, such as cadherins and tight junction proteins, highlighting the importance of the mucosal barrier in the disease process. Key to mucosal damage is the trigger of an inflammatory cascade after luminal antigen processing, a role classically ascribed to M cells in the surface follicle associated epithelium. Direct luminal antigen sampling has recently been proposed, however, by extension of dendritic cell (DC) processes through the intact gut epithelium, and it follows that early mucosal damage could result from de novo lymphoid recruitment. Cytokines, such as tumour necrosis factor alpha (TNFalpha), are known to drive inflammation, but emerging data suggest additional important roles for TNFalpha influencing mucosal barrier efficacy by altering adhesion molecule expression, influencing epithelial apoptosis, and affecting tight junction functionality.

Cadherins↗
PubMed1994

Facilitative glucose transporters.

Facilitative glucose transport is mediated by members of the Glut protein family that belong to a much larger superfamily of 12 transmembrane segment transporters. Six members of the Glut family have been described thus far. These proteins are expressed in a tissue- and cell-specific manner and exhibit distinct kinetic and regulatory properties that reflect their specific functional roles. Glut1 is a widely expressed isoform that provides many cells with their basal glucose requirement. It also plays a special role in transporting glucose across epithelial and endothelial barrier tissues. Glut2 is a high-Km isoform expressed in hepatocytes, pancreatic beta cells, and the basolateral membranes of intestinal and renal epithelial cells. It acts as a high-capacity transport system to allow the uninhibited (non-rate-limiting) flux of glucose into or out of these cell types. Glut3 is a low-Km isoform responsible for glucose uptake into neurons. Glut4 is expressed exclusively in the insulin-sensitive tissues, fat and muscle. It is responsible for increased glucose disposal in these tissues in the postprandial state and is important in whole-body glucose homeostasis. Glut5 is a fructose transporter that is abundant in spermatozoa and the apical membrane of intestinal cells. Glut7 is the transporter present in the endoplasmic reticulum membrane that allows the flux of free glucose out of the lumen of this organelle after the action of glucose-6-phosphatase on glucose 6-phosphate. This review summarizes recent advances concerning the structure, function, and regulation of the Glut proteins.

Amino Acid Sequence↗
PubMed2005

Inulin and oligofructose: impact on intestinal diseases and disorders.

A large and diverse variety of bacteria have evolved and adapted to live in the human intestinal habitat in a symbiotic arrangement that influences both physiology and pathology in the host. Symbiosis between host and flora can be optimised by prebiotics. Inulin-type fructans have been shown to improve the metabolic functions of the commensal flora. Clinical and experimental data suggest that they also improve the gut mucosal barrier. Furthermore, modulation of the trophic functions of the flora by these prebiotics could help in the prevention of inflammatory bowel diseases. The anti-inflammatory effects of inulin or oligofructose have been assessed in the rat model of distal colitis induced by dextran sodium sulphate, which histologically resembles human ulcerative colitis, and in the trinitrobenzene sulphonic acid model that resembles human Crohn's disease. Both inulin and oligofructose stimulate colonic production of SCFA and favour the growth of indigenous lactobacilli and/or bifidobacteria. These effects are associated with reduced mucosal inflammation and decreased mucosal lesion scores. Inulin has also been tested in a placebo-controlled clinical trial in patients with relapsing pouchitis. Treatment reduced endoscopic and histological parameters of inflammation of the pouch mucosa. Inulin and oligofructose may offer an opportunity to prevent chronic inflammatory intestinal disorders, and this potential should be tested in further clinical studies.

Animals↗
PubMed2001

Phosphatidylinositol 3-kinase-dependent pathways oppose Fas-induced apoptosis and limit chloride secretion in human intestinal epithelial cells. Implications for inflammatory diarrheal states.

The epithelial lining of the intestine serves as a barrier to lumenal bacteria and can be compromised by pathologic Fas-mediated epithelial apoptosis. Phosphatidylinositol (PI)3-kinase signaling has been described to limit apoptosis in other systems. We hypothesized that PI3-kinase-dependent pathways regulate Fas-mediated apoptosis and barrier function in intestiynal epithelial cells (IEC). IEC lines (HT-29 and T84) were exposed to agonist anti-Fas antibody in the presence or absence of chemical inhibitors of PI3-kinase (LY294002 and wortmannin). Apoptosis, barrier function, changes in short circuit current (DeltaI(sc)), and expression of adhesion molecules were assessed. Inhibition of PI3-kinase strongly sensitized IEC to Fas-mediated apoptosis. Expression of constitutively active Akt, a principal downstream effector of the PI3-kinase pathway, protected against Fas-mediated apoptosis to an extent that was comparable with expression of a genetic caspase inhibitor, p35. PI3-kinase inhibition sensitized to apoptosis by increasing and accelerating Fas-mediated caspase activation. Inhibition of PI3-kinase combined with cross-linking Fas was associated with increased permeability to molecules that were <400 Da but not those that were >3,000 Da. Inhibition of PI3-kinase resulted in chloride secretion that was augmented by cross-linking Fas. Confocal analyses revealed polymerization of actin and maintenance of epithelial cell adhesion molecule-mediated interactions in monolayers exposed to anti-Fas antibody in the context of PI3-kinase inhibition. PI3-kinase-dependent pathways, especially Akt, protect IEC against Fas-mediated apoptosis. Inhibition of PI3-kinase in the context of Fas signaling results in increased chloride secretion and barrier dysfunction. These findings suggest that agonists of PI3-kinase such as growth factors may have a dual effect on intestinal inflammation by protecting epithelial cells against immune-mediated apoptosis and limiting chloride secretory diarrhea.

3T3 Cells↗
PubMed1996

VIP-like immunoreactivity within neurons and perivascular neuronal processes of the human cerebral cortex.

Using indirect immunocytochemical techniques, neurons with VIP (Vasoactive Intestinal Polypeptide)-like immunoreactivity (ir) have been demonstrated in the human cerebral cortex of the parietal lobe. In all the cortical layers containing positive neurons, perivascular immunoreactive neuronal processes have been detected: in arterioles, they are located in the adventitial and smooth muscle layers; in capillaries, they establish tight anatomical relations with the endothelium-pericyte layer and the perivascular glial sheath. Bodies of positive neurons have also been seen adhering to capillary walls. The detection of perivascular VIP-like ir provides morphological evidence of the role played by this polypeptide in the regulation of the cerebral blood flow. Moreover, the relationships between immunoreactive neuronal processes and perivascular glia might corroborate the suggestion that VIP is involved in the functioning of the blood-brain barrier.

Antibodies, Monoclonal↗
PubMed2004

Differing roles of protein kinase C-zeta in disruption of tight junction barrier by enteropathogenic and enterohemorrhagic Escherichia coli.

BACKGROUND & AIMS: Enteropathogenic Escherichia coli and enterohemorrhagic E. coli harbor highly homologous pathogenicity islands yet show key differences in their mechanisms of action. Both disrupt host intestinal epithelial tight junctions, but the effects of enteropathogenic E. coli are more profound than those of enterohemorrhagic E. coli. The basis for this is not understood. The atypical protein kinase C isoform, protein kinase C-zeta, associates with and regulates the tight junction complex. The aim of this study was to compare the role of protein kinase C-zeta in the disruption of tight junctions after infection with enteropathogenic E. coli and enterohemorrhagic E. coli. METHODS: Model intestinal epithelial monolayers infected by enteropathogenic E. coli or enterohemorrhagic E. coli were used for these studies. RESULTS: Neither bisindolylmaleimide nor Gö6976, which block several protein kinase C isoforms but not protein kinase C-zeta, protected against the decrease in transepithelial electrical resistance after enteropathogenic E. coli infection. Rottlerin at concentrations that block novel and atypical isoforms, including protein kinase C-zeta, significantly attenuated the decrease in transepithelial electrical resistance. The specific inhibitory peptide, myristoylated protein kinase C-zeta pseudosubstrate, also significantly decreased the enteropathogenic E. coli -associated decrease in transepithelial electrical resistance and redistribution of tight junction proteins. In contrast to enteropathogenic E. coli, the level of protein kinase C-zeta enzyme activity stimulated by enterohemorrhagic E. coli was transient and minor, and protein kinase C-zeta inhibition had no effect on the decrease in transepithelial electrical resistance or the redistribution of occludin. CONCLUSIONS: The differential regulation of protein kinase C-zeta by enteropathogenic E. coli and enterohemorrhagic E. coli may in part explain the less profound effect of the latter on the barrier function of tight junctions.

Cell Membrane Permeability↗
PubMed1997

Peroxynitrite-induced apoptosis in human intestinal epithelial cells is attenuated by mesalamine.

BACKGROUND & AIMS: Peroxynitrite (PN), a potent oxidant, has been implicated in the pathogenesis of gut inflammation and epithelial cell apoptosis. The aim of this study was to investigate mesalamine, a standard therapy for inflammatory bowel disease, to see if it attenuates PN-induced cytotoxicity in human intestinal epithelial cells and if mesalamine directly interacts with PN or its precursor, nitric oxide. METHODS: T84 and HT29 cells were divided in several protocols: mesalamine was administered 2 hours before, simultaneously, or 30 minutes after PN. T84 cells, grown in filter chamber inserts, were used to determine if basolateral or apical administration of PN initiated apoptosis and epithelial barrier function. The effects of mesalamine on PN decomposition and NO half-life were determined. RESULTS: Mesalamine resulted in a dose-dependent decrease in PN-induced apoptosis, whether mesalamine was administered before (>10 micromol/L; IC50, 16 micromol/L), simultaneously (25-200 micromol/L; IC50, 24 micromol/L), or 30 minutes (200 micromol/L) after PN exposure. Mesalamine protected the epithelial barrier function of T84 cells against PN. Mesalamine rapidly degraded PN, whereas the half-life of NO was not affected. CONCLUSIONS: The beneficial effects of mesalamine in the treatment of inflammatory bowel disease may involve an attenuation of PN-induced cell injury and apoptosis through direct and indirect mechanisms without affecting NO levels.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

[Tissue distribution of the multidrug-resistance gene product P-glycoprotein and its physiological function].

In normal tissues, P-glycoprotein(P-gp), which is expressed in various tumor cells, is found on the luminal surface of epithelia of the kidney proximal tubule, small intestine and colon and bile canalicular face of hepatocytes, as well as, in the adrenal and capillary endothelial cells in the brain and testis. The physiological function of P-gp remains unclear but growing amounts of information suggest that it can play a important role in the absorption from intestine, elimination from liver and kidney and distribution into brain across the blood-brain barrier for many cancer chemotherapeutic agents as well as other drugs which reverse multidrug resistance. The competition for the P-gp-mediated transports in tissues and organs, which express multidrug-transporter, might lead to unsuspected drug interactions among these drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

New and better protocols for a short-term Caco-2 cell culture system.

The aim of the present study was to develop new and better protocols for a short-term Caco-2 cell culture system for use in rapid screening of intestinal drug absorption. Caco-2 cells were cultured according to several protocols for short-term cell culture to obtain monolayers. The effects of serum (fetal bovine serum, FBS) in the culture medium and of the period of cell culture on the barrier function and transporter activities of the monolayers were examined. The barrier function was estimated both from the transepithelial electrical resistance (TEER) and the permeability of [(14)C]mannitol. Transporter activities were monitored by measuring the permeability of [(14)C]glycylsarcosine for oligopeptide transporter (PepT1) and of rhodamine 123 for P-glycoprotein (P-gp). Caco-2 monolayers obtained by 3-day culture in the BIOCOAT HTS Caco-2 Assay System, developed by Becton Dickinson Bioscience, showed much higher permeability to hydrophilic compounds, such as mannitol, compared with those obtained by the standard 21-day culture system, due to the leaky structure of cell junctions. The newly developed 3-day protocol, which includes 10% FBS in the culture medium during the first day of culture, markedly enhanced TEER and lowered mannitol permeability of the monolayers. This protocol allowed us to better determine the rank order of permeability of compounds, giving results equivalent to those in the 21-day culture system. The longer culture period gave tighter monolayers, and the maximum value of TEER was obtained with 5 days in culture. However, after 5 days in culture, the integrity of monolayers decreased gradually. The highest activities of transporters, PepT1 and P-gp, in monolayers were obtained at days 5 or 6 of culture by the new protocol with FBS-containing medium. These results indicate that by a simple modification of the short-term culture protocol, it is possible to obtain Caco-2 monolayers with better barrier properties and higher activity of transporters that are equivalent to those found in the 21-day Caco-2 culture system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Apical effect of diosmectite on damage to the intestinal barrier induced by basal tumour necrosis factor-alpha.

BACKGROUND: In many digestive diseases the intestinal barrier is weakened by the release of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF alpha). AIM: To investigate the protective effect of apical diosmectite on the intestinal dysfunction induced by the proinflammatory cytokine TNF alpha. METHODS: Filter grown monolayers of the intestinal cell line HT29-19A were incubated for 48 hours in basal medium containing 10 ng/ml TNF alpha and 5 U/ml interferon-gamma (IFN gamma). Next, 1, 10, or 100 mg/ml diosmectite was placed in the apical medium for one hour. Intestinal function was then assessed in Ussing chambers by measuring ionic conductance (G) and apicobasal fluxes of 14C-mannitol (Jman), and intact horseradish peroxidase. In control intestinal monolayers, diosmectite did not significantly modify G, Jman, or intact horseradish peroxidase. RESULTS: After incubation with TNF alpha and IFN gamma, intestinal function altered, as shown by the increases compared with control values for G (22.8 (3.7) v (9.6 (0.5) mS/cm2), Jman (33.8 (7.5) v 7.56 (0.67) micrograms/h x cm2), and intact horseradish peroxidase (1.95 (1.12) v 0.14 (0.04) micrograms/h x cm2). G and Jman were closely correlated, suggesting that the increase in permeability was paracellular. Treatment with diosmectite restored al the variables to control values. CONCLUSIONS: Basal TNF alpha disrupts the intestinal barrier through the tight junctions, and apical diosmectite counteracts this disruption.

Gastrointestinal Agents↗
PubMed1982

Subcellular fractionation of human intestinal mucosa by large-scale zonal centrifugation. Localization of the lysophospholipase activity in distal ileum.

The subcellular localization of lysophospholipase activity (EC 3.1.1.5) in human ileal mucosa was studied by rate-zonal and isopycnic density-gradient centrifugation. The subcellular organelles (brush borders, basolateral membranes, lysosomes, mitochondria, and endoplasmic reticulum) were fractionated on a continuous sucrose gradient and located by assay of marker enzymes. Most lysophospholipase activity was found in the brush-border membranes, although the enzyme appeared in basolateral membranes as well. The possible physiological implications of this finding are discussed in view of that lysolecithin can impair the mucosal barrier function in the distal part of ileum. The localization of lysophospholipase to the brush-border membrane could thus serve a favourable purpose, preventing an accumulation of lysolecithin that might facilitate the absorption of potentially antigenic and toxic compounds.

Centrifugation, Density Gradient↗
PubMed1993

Regulation of cerebral blood flow--a brief review.

Cerebral blood flow is largely independent of perfusion pressure when autoregulation is intact. Cerebral circulation is regulated mainly by changes of vascular resistance. Resistance can be modulated by local-chemical and endothelial factors, by autacoids, and by release of transmitters from perivascular nerves. Local-chemical factors such as H(+)-, K(+)-, Ca(2+)-ions, adenosine, and osmolarity are involved in the regulation of cerebrovascular resistance during cortical activation and under pathological conditions such as hypoxia or ischaemia. Endothelial factors such as thromboxane A2, endothelin (ET), endothelium derived constrictor factor and endothelium derived relaxing (EDRF, identified as nitric oxide, NO) or hyperpolarizing (EDHF) factor, and prostacyclin (PGI2), can be released by physical stimuli such as shear stress or haemorrhage, by autacoids, by neurotransmitters, and by cytokines. Several of these factors (NO, PGI2, ET) can also be released from neurons and astrocytes thus enabling a coupling between parenchymal function and flow. Autacoids like histamine, bradykinin, eicosanoids, and free radicals influence cerebrovascular resistance, capacitance vessels and the permeability of the blood-brain barrier under pathological conditions. They are released by trauma, ischaemia, seizures and inflammation. Cerebral arteries are innervated by several systems. The sympathetic-noradrenergic fibres originate from the superior cervical ganglion. By releasing the constricting transmitters norepinephrine and neuropeptide Y this system extends the range of autoregulation. The parasympathetic cholinergic system with the dilating transmitters acetylcholine and vasoactive intestinal polypeptide may prevent ischaemia. Besides the intracerebral noradrenergic and serotonergic perivascular innervation with an unclear function, a trigeminal innervation has been described.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Physiological role of mucins in the colonic barrier integrity].

Colonic mucus is a key element of colonic barrier as it is located at the frontier between luminal microflora and colonic mucosa itself. Colonic mucus is mainly composed of high molecular weight glycoproteins called mucins that can be either secreted or membrane-linked. The expression of various colonic mucins is altered in colorectal cancers or inflammations. The aim of this review is to highlight the crucial role played by colonic mucins in the maintenance of colonic barrier integrity, both because they are part of the protective mucus layer, and because they individually exert specific functions involved in epithelial barrier, like cell growth and differentiation, immunomodulation, signal transduction or cell adhesion.

Bacterial Translocation↗