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At least 73 records · Page 4Linked to original sources
PubMed2002

The influence of apoptosis of mucosal epithelial cells on intestinal barrier integrity after scald in rats.

OBJECTIVE: To study the influence of apoptosis of intestinal epithelial cells occurring as a result of reperfusion after burn shock on the intestinal barrier. METHODS: Fifty Wistar rats were subjected to a 30% TBSA full thickness burn, and normal saline (40 ml/kg) was given intraperitoneally immediately after the injury (group A). Ten rats served as a sham control group. The experimental group B consisted of 50 rats with identical injuries, but the normal saline was not given until 6h after the injury. Apoptosis of intestinal epithelial cells was verified by DNA fragmentation, DNA agarose gel electrophoresis, TUNEL and electron microscope (EM), and DNA fragmentation rate was expressed as ap%. The D-lactic acid in portal vein blood and intestinal diamine oxidase (DAO) were determined to evaluate the permeability and integrity of intestinal mucosal epithelium. RESULTS: The ap% of intestinal epithelium group B was higher than in that of group A (P<0.05 or 0.01), and its amplitude peaked at 12h for both groups. Typical DNA ladder pattern was seen in electrophoresis in both groups. Apoptotic cells were discerned on the tips of the ileal villi at 3h postscald by TUNEL and EM in the group B, and they appeared earlier than in the group A. There was a significant positive correlation between the ap% and the level of D-lactic acid (group A: r=0.817, P<0.05; group B: r=0.727, P<0.05). On the other hand, a significant negative correlation was found between the ap% and the DAO values (group A: r=-0.937, P<0.01; group B: r=-0.836, P<0.05). CONCLUSION: Apoptosis occurred in enterocytes after scald injury this pathological change might contribute to a breach of integrity of intestinal epithelium, leading to a compromise in its barrier function. Delayed fluid resuscitation might lead to an earlier and higher degree of apoptosis of the intestinal epithelial cells.

Amine Oxidase (Copper-Containing)↗
PubMed2006

Stress-induced breakdown of intestinal barrier function in the rat: reversal by wood creosote.

Our previous studies demonstrated that wood creosote (Seirogan) inhibits intestinal secretion and normalizes the transport of electrolytes and water in rats subjected to restraint stress. The goal of the present study was to examine whether wood creosote has a protective effect against stress-induced breakdown of intestinal barrier function. F-344 rats were subjected to 90-min water avoidance stress (WAS) with wood creosote (30 mg/kg) or vehicle administered intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote or vehicle treatment but did not experience the WAS. All rats were euthanized at the end of the WAS or sham-stress and the jejunum and colon were isolated. Epithelial transport was studied in modified Ussing chambers. Spontaneous secretion was assessed by electrophysiological measurement of the short circuit current (I(sc)) while electrical conductance (G) was calculated from the potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS significantly elevated basal I(sc) and G and increased epithelial permeability to HRP in the jejunum but not in the colon. Wood creosote resulted in a significant reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal flux of HRP compared to the vehicle-treated group. Wood creosote caused no significant effects in sham-stressed rats. The results suggest that oral administration of wood creosote may prevent stress-induced diarrhea by preventing aversive effects on small intestinal secretion and barrier function.

Animals↗
PubMed1997

Bacterial lipopolysaccharide reduced intestinal barrier function and altered localization of 7H6 antigen in IEC-6 rat intestinal crypt cells.

The intestinal epithelial barrier restricts the passage of potentially toxic substances into the systemic circulation and is considered to be mostly mediated by tight junctions, though the mechanisms involved in the regulation of intestinal tight junctions are not yet fully understood. In the present study, we examined whether bacterial lipopolysaccharide (LPS) altered the barrier function of tight junction and localization of tight junctional proteins, ZO-1 and 7H6 antigen, in IEC-6 intestinal cells. Administration of LPS to the basolateral surface of IEC-6 cells disrupted the barrier function and caused the disappearance of 7H6 antigen from the cell border, whereas LPS administered to the apical surface altered neither the barrier function nor the localization of 7H6 antigen in IEC-6 cells. On the other hand, the localization of ZO-1 was not influenced by these treatments of LPS. These results suggest that the interaction of LPS with the basolateral surface of intestinal epithelial cells disrupts the barrier function and 7H6 antigen take part in the maintenance of the barrier function in IEC-6 cells.

Animals↗
PubMed2006

[Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy].

OBJECTIVE: To study the protective effect of glutamine (Gln) on intestinal permeability in patients receiving chemotherapy. METHODS: Thirty-nine patients with gastrointestinal cancer after operation were randomly divided into Gln and control groups, and received oral administration of glutamine (30 g/d) for 7 days (n=22) or not (n=17). All patients received CF+ 5-FU chemotherapy for 5 days. Serum concentration of glutamine and urinary lactulose/mannitol (L/M) ratio were measured before and 1 day after chemotherapy. RESULTS: After chemotherapy, the serum Gln concentration was significantly decreased to (535.42+/- 53.75) micromol/L in the control group and increased to (54.44+/- 81.26) micromol/L in the Gln group, and there was significant difference between the two groups (P< 0.01). Urine L/M ratio was significantly increased to (0.0453+/- 0.0078) in the control group and decreased to (0.0331+/- 0.0061) in the Gln group, and there was significant difference between the two groups after chemotherapy (P< 0.01). CONCLUSION: Oral administration of glutamine granules can increase serum concentration of glutamine in chemotherapy patients with gastrointestinal cancer and can decrease intestinal permeability, maintain intestinal barrier.

Aged↗
PubMed2002

Nitric oxide directly impairs intestinal barrier function.

Excess production of nitric oxide (NO) has been implicated in endotoxin-induced loss of gut barrier function in vivo. Thus, we tested the direct effect of NO on the barrier function of intestinal mucosal membranes suspended ex vivo in Ussing chambers and on IEC-6 enterocyte monolayers. In these experiments, ex vivo-mounted ileal membranes or IEC-6 cell enterocyte monolayers were exposed to the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP) over a dose range (10 microm to 2 mM) or medium. SNAP at concentrations of 1 or 2 mM, but not 10 or 100 microM, increased the rates of bacterial translocation (BT) across both the ileal membranes and the IEC-6 monolayers by >1 log (P < 0.05), as well as the permeability of the IEC-6 monolayers to phenol red (P < 0.05). The ileal membranes exposed to 1 or 2 mM SNAP for 3 h manifested histologic evidence of mucosal injury and decreases in electrical resistance and potential difference values (P < 0.05), while the IEC-6 cells exposed to SNAP for 18 h had increased levels of cell death (P < 0.05). Since NO produced locally by stimulated enterocytes could contribute to barrier dysfunction, NO production, iNOS mRNA levels, and monolayer permeability were measured in enterocytes (IEC-6 and Caco-2) exposed to medium, endotoxin (lipopolysaccharide [25 microg/mL]) or a cytokine mixture (IL-1beta 10 ng/mL, TNF-alpha 10 ng/mL, and INF-gamma 250 U/mL) for 6 or 24 h. Endotoxin increased NO production, iNOS mRNA expression, and monolayer permeability in the IEC-6, but not the Caco-2 cells, while exposure to the cytokine mixture increased both NO production, iNOS mRNA expression, and monolayer permeability in both the IEC-6 and Caco-2 cell lines. Based on the results of these studies it appears that NO can directly increase ileal mucosal membrane and enterocyte monolayer permeability and BT and that increased NO production and iNOS mRNA expression is associated with endotoxin- and/or cytokine-induced loss of enterocyte monolayer barrier function.

Animals↗
PubMed2004

Ursodeoxycholic acid ameliorates experimental ileitis counteracting intestinal barrier dysfunction and oxidative stress.

The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) on intestinal permeability (IP) and reactive oxygen species (ROS) generation in indomethacin-induced enteropathy, a well-known experimental model of Crohn's disease. Seventy-eight male Wistar rats were randomly assigned to receive indomethacin, indomethacin + UDCA, or vehicles. Indomethacin induced a significant increase in the fraction of urinary excretion of 51Cr-EDTA following oral administration (7.9 +/- 1.3 vs 2.3 +/- 0.2%; P < 0.05) and lucigenin-amplified chemiluminescence in intestinal fragments ex vivo (10.1 +/- 1.9 vs 2.6 +/- 0.4 cpm x 10(3)/mg; P < 0.05) compared to controls. UDCA significantly reversed these effects (P < 0.05), without being incorporated in biliary bile acid composition (HPLC analysis). These findings support a local protective effect of UDCA in experimental ileitis by the modulation of intestinal barrier dysfunction and oxidative stress. In short, they provide insights into mechanisms of action of UDCA in intestinal inflammation and a new perspective on the treatment of Crohn's disease.

Animals↗
PubMed1996

Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage.

Intestinal mucosal barrier function in obstructive jaundice was assessed in an animal model and in patients. The effect of internal biliary drainage in patients was also examined. Bile duct ligation for 1 week in the rat resulted in significant bacterial translocation (in seven of 12 animals following ligation versus none of the shamoperated controls, P < 0.01). Intestinal permeability, measured by the urinary recovery of orally administered polyethylene glycol, was also significantly increased (+66.2 per cent for ligation versus -11.6 per cent for sham, P < 0.01). A prospective study was performed on 33 patients with obstructive jaundice undergoing internal biliary drainage, and results were compared with those in six non-jaundiced patients undergoing laparotomy or endoscopic retrograde cholangiopancreatography and in 11 health volunteers. The lactulose: mannitol ratio was used as an intestinal permeability index. Mean(s.e.m.) intestinal permeability assessed before operation was significantly increased in jaundiced patients compared with control patients (0.050(0.010) versus 0.016(0.003), P < 0.005). The mean(s.e.m.) lactulose: mannitol ratio in the healthy volunteers was 0.020(0.003), which was similar to that in control patients. In the jaundiced group of patients the intestinal permeability index fell to within normal levels after 28 days of internal biliary drainage (0.050 before operation versus 0.021 at 28 days, P < 0.02). These data indicate that intestinal barrier function is impaired in obstructive jaundice and that this impairment is reversed by return of bile to the gastrointestinal tract.

Animals↗
PubMed2005

The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics.

The human intestinal Caco-2 cell line has been extensively used over the last twenty years as a model of the intestinal barrier. The parental cell line, originally obtained from a human colon adenocarcinoma, undergoes in culture a process of spontaneous differentiation that leads to the formation of a monolayer of cells, expressing several morphological and functional characteristics of the mature enterocyte. Culture-related conditions were shown to influence the expression of these characteristics, in part due to the intrinsic heterogeneity of the parental cell line, leading to selection of sub-populations of cells becoming prominent in the culture. In addition, several clonal cell lines have been isolated from the parental line, exhibiting in general a more homogeneous expression of differentiation traits, while not always expressing all characteristics of the parental line. Culture-related conditions, as well as the different Caco-2 cell lines utilized in different laboratories, often make it extremely difficult to compare results in the literature. This review is aimed at summarizing recent, or previously unreviewed, data from the literature on the effects of culture-related factors and the influence of line sub-types (parental vs. different clonal lines) on the expression of differentiation traits important for the use of Caco-2 cells as a model of the absorptive and defensive properties of the intestinal mucosa. Since the use of Caco-2 cells has grown exponentially in recent years, it is particularly important to highlight these methodological aspects in order to promote the standardization and optimisation of this intestinal model.

Autocrine Communication↗
PubMed2000

[Observation of the modulatiny effect of histamine on intestinal barrier function].

The model of CaCo2 cell monolayer system has been generally accepted as a standard method for in vitro study of the relationship between the epithelium and microbial invasion. In this study, we set up the model with a simplified method and used it to observe if histamine, which is an important inflammatory factor in gastroenteric tract, can offer some barrier protection from E. coli invasion. After two weeks' routine incubation, the established CaCo2 cells monolayer systems were co-cultured with 1 x 10(-8) mmol/L, 1 x 10(-7) mmol/L and 1 x 10(-6) mmol/L histamine DMEM for 2 hours, and with frank DMEM as control for the same length of the time. For observation on time course effect of histamine, the co-cultures with 1 x 10(-6) mmol/L histamine DMEM were kept up for 0.5, 1.0, 2.0, 4.0 and 18.0 hours. Bacterial invasion ws assessed by quantitating the number of E. coli within the coultured epithelial cells. The results showed that histamine significantly inhibited the invasion of E. coli to epithelial cells(P < 0.05). The colony counts in co-cultures with 1 x 10(-7) mmol/L and 1 x 10(-8) mmol/L histamine DMEM were 52.5, 30.3 and 91.3 respectively, compared with 563 in control group. In the study of the time course effect of histamine, the colony conuts of co-culture with histamine DMEM for 0.5, 1.0, 2.0, 4.0 and 18.0 hours were 135.5, 64.0, 29.5, 36.0 and 22.5 respectively. It was concluded that histamine can enhance the protective barrier function of intestinal epithelium against E. coli invasion.

Bacterial Translocation↗
PubMed2005

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.

Amino Acid Sequence↗
PubMed2002

Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure.

BACKGROUND & AIMS: Enteric infections have been implicated in the pathogenesis of both food intolerance and autoimmune diseases secondary to the impairment of the intestinal barrier. On the basis of our recent discovery of zonulin, a modulator of small-intestinal tight junctions, we asked whether microorganisms might induce zonulin secretion and increased small-intestinal permeability. METHODS: Both ex vivo mammalian small intestines and intestinal cell monolayers were exposed to either pathogenic or nonpathogenic enterobacteria. Zonulin production and changes in paracellular permeability were monitored in Ussing chambers and micro-snapwells. Zonula occludens 1 protein redistribution after bacteria colonization was evaluated on cell monolayers. RESULTS: Small intestines exposed to enteric bacteria secreted zonulin. This secretion was independent of either the species of the small intestines or the virulence of the microorganisms tested, occurred only on the luminal aspect of the bacteria-exposed small-intestinal mucosa, and was followed by a decrease in small-intestinal tissue resistance (transepithelial electrical resistance). The transepithelial electrical resistance decrement was secondary to the zonulin-induced tight junction disassembly, as also shown by the disengagement of the protein zonula occludens 1 protein from the tight junctional complex. CONCLUSIONS: This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms and contributes to the host response against bacterial colonization of the small intestine.

Animals↗
PubMed2003

Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.

BACKGROUND AND AIMS: Despite the progress made in understanding the immunological aspects of the pathogenesis of coeliac disease (CD), the early steps that allow gliadin to cross the intestinal barrier are still largely unknown. The aim of this study was to establish whether gliadin activates a zonulin dependent enterocyte intracellular signalling pathway(s) leading to increased intestinal permeability. METHODS: The effect of gliadin on the enterocyte actin cytoskeleton was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence microscopy and spectrofluorimetry. Zonulin concentration was measured on cell culture supernatants by enzyme linked immunosorbent assay. Transepithelial intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in Ussing chambers. RESULTS: Incubation of cells with gliadin led to a reversible protein kinase C (PKC) mediated actin polymerisation temporarily coincident with zonulin release. A significant reduction in Rt was observed after gliadin addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment with the zonulin inhibitor FZI/0 abolished the gliadin induced actin polymerisation and Rt reduction but not zonulin release. CONCLUSIONS: Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight junction opening leads to a rapid increase in intestinal permeability.

Actins↗
PubMed2003

Impact of perioperative treatment of recombinant human growth hormone on cell immune function and intestinal barrier function: randomized, double-blind, controlled trial.

The objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo-controlled randomized double-blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin-like growth factor-1 (IGF-1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF-1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation ( p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values ( p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation-related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients.

Adult↗
PubMed2005

Intestinal barrier function and weight gain in malnourished children taking glutamine supplemented enteral formula.

OBJECTIVE: We examined the effect of standard formula and glutamine or glycine supplemented enteral formula on intestinal permeability and weight gain in children with malnutrition. METHODS: 80 children aged 2 to 60 months with a weight-for-age z-score less than -- 2 were studied. From December 1996 to April 1999, 27 study patients received nonsupplemented formula. From June 2001 to June 2002 an additional 53 patients were randomly assigned to receive formula supplemented with glutamine or glycine (isosmolar concentrations) for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed before and after 10 days of nutritional rehabilitation. Weight was measured before and after treatment. RESULTS: Patients were similar on admission with regard to age, sex, nutritional status and lactulose/mannitol ratio. The lactulose/mannitol ratio significantly improved (decreased) in children receiving formula supplemented with glutamine for 10 days but not in those receiving glycine or nonsupplemented formula. Weight gain occurred during therapy in all groups and was not statistically different among groups. CONCLUSION: Formula supplemented with glutamine improves intestinal barrier function compared with nonsupplemented formula but does not augment weight gain.

Child Nutrition Disorders↗
PubMed1994

Effect of acute Yersinia enterocolitica infection on intestinal barrier function in the mouse.

BACKGROUND: Yersinia enterocolitica is an important cause of diarrhea, but little is known about the underlying mechanisms. We therefore studied the impact of acute Y. enterocolitica infection on intestinal barrier function in a mouse model. METHODS: For this purpose CD-1 mice were infected with Y. enterocolitica (serotype 08; 6 x 10(7) viable bacteria), and alternating current impedance analysis was performed on days 1, 2, 3, 5, and 8 after infection. RESULTS: The infection resulted in a decrease in epithelial resistance from 18.0 +/- 0.9 omega.cm2 (controls) to 12.1 +/- 0.5 omega.cm2 (day 1, p < 0.001), from which the animals recovered by day 5. To locate this loss in barrier function, the horizontal distribution of local conductances was measured by voltage scanning, yielding two results. First, conductance was homogeneously distributed across the chamber area, excluding erosions or ulcers among the gross surface area and favoring tight junction opening as the source of barrier dysfunction. Second, the conductance of villus tips was compared with that of the intervillus region (consisting of lateral villus walls plus crypts). On day 1 the former was increased by 74% and the latter by 18%. Then, two other mechanisms of diarrhea were tested, namely malabsorption and secretion. First, the increase in ISC after the addition of 3-O-methylglucose, representing Na(+)-glucose cotransport, was shown not to be impaired. Second, bumetanide-inhibitable ISC, representing electrogenic Cl- secretion, also did not differ between controls and infected animals. CONCLUSIONS: Our data show that epithelial barrier dysfunction plays a role in Y. enterocolitica infection, while Na(+)-glucose cotransport and electrogenic Cl- secretion are unaltered.

Acute Disease↗
PubMed2000

Apoptosis and intestinal barrier function.

The signal transduction pathways of the induction of apoptosis in the gastrointestinal tract have in part been discovered. However, almost nothing is known about the functional influence of apoptotic signals on intestinal barrier function. In this study the effect of camptothecin-induced apoptosis in HT-29/B6 monolayers and the influence of apoptosis on epithelial barrier function were characterized. We demonstrated that camptothecin causes a decrease of transepithelial resistance and an increase in fluxes of the paracellular marker [3H]mannitol. Camptothecin increased the apoptotic rate and the conductance of single-cell apoptosis as measured by the conductance scanning technique. We conclude that in our model of HT-29/B6 cells camptothecin is a potent inductor of apoptosis that causes significant barrier defects measured by the Ussing chamber technique and the conductance scanning technique. Based on these results we are able to investigate the effect of other cytokines--TGF-beta, for instance, and its role in apoptotic conditions.

Apoptosis↗
PubMed1997

Effect of oral supplementation of ornithine-alpha-ketoglutarate on the intestinal barrier after orthotopic small bowel transplantation.

The aim of this study was to analyze the possible protective effects of a glutamine and arginine precursor (ornithine-alpha-ketoglutarate [OKG]) on the mucosa of a transplanted intestine when administered with either a defined formula oral diet (DFD) or a standard chow. Isogenic male Lewis rats (250 g) were submitted to a laparotomy (groups 1 and 2) or to an orthotopic small bowel transplantation (SBT; groups 3-6). Groups 1, 3, and 5 received a DFD 14 days after surgery. Groups 2, 4, and 6 received standard chow. In addition, groups 5 and 6 received a daily oral supplementation of 1.4 g/kg of OKG. Weight changes and food intake were recorded daily. At the end of the study, bacterial translocation (BT) was measured in mesenteric lymph nodes, liver, and spleen. The protein/DNA index was also determined in intestinal mucosa. SBT induced BT in all transplanted groups, especially in those fed DFD. Addition of OKG (groups 5 and 6) significantly reduced BT in comparison with groups 3 and 4 and improved the protein/DNA index as well as weight gain. It is concluded that OKG supplementation protects the intestinal barrier after SBT, and that this effect is more marked when it is added to a standard chow.

Animals↗
PubMed2006

The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock.

The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of numerous conditions associated with excessive inflammation. To determine whether RAGE-dependent signaling is important in the development of intestinal barrier dysfunction after hemorrhagic shock and resuscitation (HS/R), C57Bl/6, rage(-/-), or congenic rage(+/+) mice were subjected to HS/R (mean arterial pressure of 25 mmHg for 3 h) or a sham procedure. Twenty-four hours later, bacterial translocation to mesenteric lymph nodes and ileal mucosal permeability to FITC-labeled dextran were assessed. Additionally, samples of ileum were obtained for immunofluorescence microscopy, and plasma was collected for measuring IL-6 and IL-10 levels. HS/R in C57Bl/6 mice was associated with increased bacterial translocation, ileal mucosal hyperpermeability, and high circulating levels of IL-6. All of these effects were prevented when C57Bl/6 mice were treated with recombinant human soluble RAGE (sRAGE; the extracellular ligand-binding domain of RAGE). HS/R induced bacterial translocation, ileal mucosal hyperpermeability, and high plasma IL-6 levels in rage(+/+) but not rage(-/-) mice. Circulating IL-10 levels were higher in rage(-/-) compared with rage(+/+) mice. These results suggest that activation of RAGE-dependent signaling is a key factor leading to gut mucosal barrier dysfunction after HS/R.

Animals↗