Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier.

Background: Food allergy and chronic intestinal inflammation are common in western countries. The complex of antigen/IgE is taken up into the body from the gut lumen with the aid of epithelial cell-derived CD23 (low affinity IgE receptor II) that plays an important role in the pathogenesis of intestinal allergy. This study aimed to elucidate the role of mast cell on modulation of antigen/IgE complex transport across intestinal epithelial barrier.

Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction.

Background: Psychological stress is one of the factors associated with many human diseases; the mechanisms need to be further understood.

Methods: Rats were subjected to chronic water avoid stress. Intestinal epithelial heat shock protein (HSP) 70 was evaluated.

CD83+CCR7- dendritic cells accumulate in the subepithelial dome and internalize translocated Escherichia coli HB101 in the Peyer's patches of ileal Crohn's disease.

Recurrent Crohn's disease originates with small erosions in the follicle-associated epithelium overlying the Peyer's patches. Animal studies have illustrated mucosal immune regulation by dendritic cells located in the subepithelial dome. The aim of this study was to characterize the dendritic cells at this specific site in patients with Crohn's disease.

Stress neuropeptides evoke epithelial responses via mast cell activation in the rat colon.

Background: Previously, we showed that corticotropin-releasing factor (CRF) injected i.p. mimicked epithelial responses to stress, both stimulating ion secretion and enhancing permeability in the rat colon, and mast cells were involved.

The role of luminal factors in the recovery of gastric function and behavioral changes after chronic Helicobacter pylori infection.

The role of chronic infections, such as Helicobacter pylori (Hp), to produce sustained changes in host physiology remains controversial. In this study, we investigate whether the antigenic or bacterial content of the gut, after Hp eradication, influences the changes in gut function induced by chronic Hp infection. Mice were infected with Hp for 4 mo and then treated with antibiotics or placebo for 2 wk.

Chronic peripheral administration of corticotropin-releasing factor causes colonic barrier dysfunction similar to psychological stress.

Chronic psychological stress causes intestinal barrier dysfunction and impairs host defense mechanisms mediated by corticotrophin-releasing factor (CRF) and mast cells; however, the exact pathways involved are unclear. Here we investigated the effect of chronic CRF administration on colonic permeability and ion transport functions in rats and the role of mast cells in maintaining the abnormalities. CRF was delivered over 12 days via osmotic minipumps implanted subcutaneously in wild-type (+/+) and mast cell-deficient (Ws/Ws) rats.

Pathophysiological mechanisms of stress-induced intestinal damage.

Stress has been shown to have both central and peripheral effects, promoting psychological illness (such as anxiety and depression), as well influencing peripheral disease in the intestine. Stress in humans can exacerbate symptoms of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), lowering visceral pain thresholds and decreasing mucosal barrier function. Studies in rodents have revealed that both acute and chronic exposure to stressors can lead to pathophysiology of the small and large intestine, including altered ion secretion and increased epithelial permeability (by both transcellular and paracellular pathways).

Intestinal epithelial barrier dysfunction and dendritic cell redistribution during early stages of inflammation in the rat: role for TLR-2 and -4 blockage.

Background: Dendritic cell (DC) redistribution during early stages of enteritis may be related to ileal barrier dysfunction. We used a rat model of ileitis to examine this hypothesis.

Methods: Sprague-Dawley rats were injected with indomethacin or saline and euthanized 2, 6, 12, or 24 hours later.

Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenic E. coli is enhanced by TNF-alpha.

A defect in mitochondrial activity contributes to many diseases. We have shown that monolayers of the human colonic T84 epithelial cell line exposed to dinitrophenol (DNP, uncouples oxidative phosphorylation) and nonpathogenic Escherichia coli (E. coli) (strain HB101) display decreased barrier function.

Dendritic cells and toll-like receptors 2 and 4 in the ileum of Crohn's disease patients.

We investigated myeloid-dendritic cell (DC) marker and Toll-like receptor (TLR)-2 and 4 distributions in ileal samples from Crohn's disease (CD) patients (n = 14) and controls (n = 13). In controls, no TLR-2+ cells were observed, and higher numbers of TLR-4+ and DC-SIGN+ cells (P < 0.01) were detected in ileal samples when compared versus colonic tissues.

Neonatal maternal separation of rat pups results in abnormal cholinergic regulation of epithelial permeability.

Neonatal maternal separation (MS) predisposes adult rats to develop stress-induced mucosal barrier dysfunction/visceral hypersensitivity and rat pups to develop colonic epithelial dysfunction. Our aim was to examine if enhanced epithelial permeability in such pups resulted from abnormal regulation by enteric nerves. Pups were separated from the dam for 3 h/day (days 4-20); nonseparated (NS) pups served as controls.

Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation.

Background: We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long-term changes in intestinal physiology.

Aim: To examine if administration of probiotics affects MS-induced gut dysfunction.

Methods: MS pups were separated from the dam for 3 h/day from days 4 to 19; non-separated (NS) pups served as controls.

Chronic psychological stress alters epithelial cell turn-over in rat ileum.

Dysregulated epithelial cell kinetics associated with mucosal barrier dysfunction may be involved in certain intestinal disorders. We previously showed that chronic psychological stress, in the form of repetitive sessions of water avoidance stress (WAS), has a major detrimental impact on ileal barrier function. We hypothesized that these changes were related to a disturbance in enterocyte kinetics.

Psychological stress impairs Na+-dependent glucose absorption and increases GLUT2 expression in the rat jejunal brush-border membrane.

Chronic psychological stress impacts many functions of the gastrointestinal tract. However, the effect of stress on nutrient absorption is poorly documented. This study was designed to investigate glucose transporters in rats submitted to different periods of water-avoidance stress (WAS).

Correlation between cyclical epithelial barrier dysfunction and bacterial translocation in the relapses of intestinal inflammation.

Background: Although several factors have been implicated in the pathogenesis of inflammatory bowel disease (IBD), the mechanisms underlying the recurrent relapses have not yet been clarified. We hypothesized that epithelial barrier dysfunction, associated with intestinal motor disturbances, could play a key role in exacerbation of inflammatory illness due to an increased uptake of luminal antigen and bacterial translocation.

Methods: Indomethacin administration to rats induced a long-lasting oscillation of active and quiescent phases of inflammation associated with phases of hypo and hypermotility.

CD23-mediated transport of IgE/immune complexes across human intestinal epithelium: role of p38 MAPK.

We previously reported that CD23/FcepsilonRII (low-affinity IgE receptor) is expressed on human intestinal epithelial cells and is responsible for transepithelial transport of IgE. In this study, we compared the transport of IgE with that of immune complexes in both the apical-to-serosal and the serosal-to-apical directions across HT29 epithelial cell layers and examined the effects of two p38 MAPK inhibitors, SKF86002 and SB203580, on the expression and function of CD23. Our study showed that both p38 MAPK inhibitors at 10 microM significantly inhibited constitutive and IL-4-upregulated CD23 protein expression in epithelial cells.

Characterization of ileal dendritic cell distribution in a rat model of acute and chronic inflammation.

We examined ileal dendritic cell (DC) subpopulations in a rat model of indomethacin-induced enteritis to determine changes in phenotype and distribution associated with increased mucosal permeability during acute and chronic stages of inflammation. Sprague-Dawley rats were treated with indomethacin (7.5 mg/kg subcutaneously, 2 injections 48 h apart).

Chronic psychological stress in rats induces intestinal sensitization to luminal antigens.

There is increasing evidence that stress plays a role in the pathophysiology of chronic intestinal disorders, but the mechanisms remain unclear. Previous studies in rats have revealed that stress decreases gut barrier function and allows excessive uptake of luminal material. Here, we investigated whether chronic psychological stress acts to induce sensitization of intestinal tissues to oral antigens.

Enterocyte cytoskeleton changes are crucial for enhanced translocation of nonpathogenic Escherichia coli across metabolically stressed gut epithelia.

Substantial data implicate the commensal flora as triggers for the initiation of enteric inflammation or inflammatory disease relapse. We have shown that enteric epithelia under metabolic stress respond to nonpathogenic bacteria by increases in epithelial paracellular permeability and bacterial translocation. Here we assessed the structural basis of these findings.

Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance.

Previous studies have shown that early life stress in the form of intermittent maternal separation (MS) predisposes adult rats to develop stress-induced intestinal mucosal dysfunction and visceral hypersensitivity. However, the mechanism involved in the functional abnormalities is unclear. Our aim was to study immature animals during or shortly after exposure to MS to determine whether there are early pathophysiological changes in the gut.

Novel effects of the prototype translocating Escherichia coli, strain C25 on intestinal epithelial structure and barrier function.

Intestinal bacteria play an etiologic role in triggering and perpetuating chronic inflammatory bowel disorders. However, the precise mechanisms whereby the gut microflora influences intestinal cell function remain undefined. Therefore, the effects of the non-pathogenic prototype translocating Escherichia coli, strain C25 on the barrier properties of human T84 and Madine-Darby canine kidney type 1 epithelial cells were examined.

CD23-mediated IgE transport across human intestinal epithelium: inhibition by blocking sites of translation or binding.

Background & Aims: In previous studies in rodent models of food allergy, we identified that sensitization induces expression of CD23 on intestinal epithelial cells and results in enhanced IgE-dependent transepithelial antigen uptake; further studies in CD23-/- mice provided evidence that CD23 is involved in protected transport of antigen into the body. Little information exists in humans on receptor-mediated immunoglobulin (Ig)E transport across epithelia. The present study was designed to examine expression of CD23 by human epithelial cells, determine its isoform and regulation by interleukin (IL) 4, and identify the role of CD23 in transepithelial IgE transport.

Eradication of Helicobacter spp. from a rat breeding colony.

Although Helicobacter spp. have been viewed as bacteria with low pathogenicity, many investigators have shown that these low-grade pathogens have the potential to become a severe threat in immunocompromised, inbred, and transgenic animals. Therefore the presence of Helicobacter spp.

Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins.

Tight junctions between intestinal epithelial cells prevent ingress of luminal macromolecules and bacteria and protect against inflammation and infection. During stress and inflammation, mast cells mediate increased mucosal permeability by unknown mechanisms. We hypothesized that mast cell tryptase cleaves protease-activated receptor 2 (PAR2) on colonocytes to increase paracellular permeability.

Intracellular trafficking of CD23: differential regulation in humans and mice by both extracellular and intracellular exons.

In mouse models of food allergy, we recently characterized a new CD23b-derived splice form lacking extracellular exon 5, bDelta5, which undergoes constitutive internalization and mediates the transepithelial transport of free IgE, whereas classical CD23b is more efficient in transporting IgE/allergen complexes. These data suggested that regulation of endocytosis plays a central role in CD23 functions and drove us to systematically compare the intracellular trafficking properties of human and murine CD23 splice forms. We found that CD23 species show similar endocytic behaviors in both species; CD23a undergoes constitutive clathrin-dependent internalization, whereas CD23b is stable at the plasma membrane.