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PubMed2004

Mechanisms of postburn intestinal barrier dysfunction in the rat: roles of epithelial cell renewal, E-cadherin, and neutrophil extravasation.

OBJECTIVE: Our group has previously shown that the intestinal epithelium exhibits increased postburn barrier permeability and bacterial translocation associated with deranged neutrophil activity. The purpose of this investigation is to explore possible underlying intestinal structural mechanisms, leading to those functional changes with emphasis on (1) neutrophil influx and extravasation in the intestinal lamina propria 1-3 days after burn and (2) enterocyte proliferation, migration, apoptosis, and E-cadherin junctional epithelium levels 3 days after burn. DESIGN: Freshly isolated ileum specimens were quick frozen, then cut by a cryostat into 30-micron-thick sections. Sections from day 1 postburn rats were immunostained with (1) anti-granulocyte or anti-elastase antibodies to assess neutrophil influx or (2) combined anti-granulocyte and anti-von Willebrand factor double immunolabeling to compare levels of neutrophil extravasation. Sections from day 3 postburn rats were immunostained with (1) bromodeoxyuridine immunohistochemistry 1, 3, 6, or 18 hrs after bromodeoxyuridine injection to assess enterocyte proliferation and migration, (2) cytokeratin-18 M30-immunohistochemistry to compare levels of enterocyte apoptosis, and (3) E-cadherin immunohistochemistry to compare junctional E-cadherin integrity. Ileal myeloperoxidase activity and bacterial translocation of Enterococcus faecalis were assessed biochemically and by E. faecalis-specific bacterial cultures, respectively, in day 3 postburn rats. SETTING: : Research laboratories in a medical center and an academic institution. SUBJECTS: Male Sprague-Dawley rats given sham treatment or treatment as a burn model with full-thickness skin scald over 30% total body surface area. CONCLUSIONS: We report (1) increased levels of neutrophil influx and extravasation in villi lamina propriae, including elastase-positive cells (postburn day 1), (2) heightened levels of intestinal myeloperoxidase activity (postburn day 3), (3) decreased levels of epithelial cell proliferation, migration, and E-cadherin (postburn day 3), and (4) increased enterocyte apoptosis and E. faecalis bacterial translocation (postburn day 3). Based on these structural and functional abnormalities, we propose a mechanism for burn injury-related intestinal barrier dysfunction that includes increased trans- and para-cellular leakage caused by impaired enterocyte renewal and decreased junctional E-cadherin levels subsequent to increased neutrophil influx and extravasation within the villus lamina propria microenvironment.

Animals↗

PubMed1996

Paneth cell defensins: endogenous peptide components of intestinal host defense.

Paneth cells are epithelial granulocytes at the base of the crypts of Lieberkühn in the small intestine of many mammalian species. These secretory cells contribute to mucosal barrier function by the apical release of granules containing a variety of antimicrobial products, including peptides termed cryptdins, for crypt defensins. In mice, six Paneth cell defensins have been characterized at the peptide level that have potent antimicrobial activities equivalent to or greater than that of rabbit neutrophil defensin NP-1. Cryptdin peptides that differ only by single amino acid substitutions have been shown to exhibit a high degree of specificity against certain target microorganisms. Cryptdins are coded by separate, two-exon genes that are located on chromosome 8 in both mice and humans. Human Paneth cells contain high levels of two different defensin mRNAs, but in mice at least 19 cryptdin isoforms are predicted from cDNA sequencing data. The mouse cryptdin-4 gene is expressed with positional specificity along the longitudinal intestinal axis, and cryptdin genes are active in the intestinal epithelium prior to Paneth cell differentiation. Accordingly, Paneth cell defensins are early markers of crypt ontogeny and are therefore useful in studies of lineage determination in the intestinal epithelium. Because cryptdins mediate innate immunity in the hostile environment of the intestinal lumen, it should be of interest to define biochemical and biophysical attributes that adapt these peptides to barrier function of mucosal surfaces.

Amino Acid Sequence↗

PubMed1988

The gut: a central organ after surgical stress.

The intestinal tract plays a central role in the protein catabolic response after injury and infection. The mucosa utilizes glutamine and thus spares glucose--presumably sparing this essential fuel source for tissues with an obligate glucose requirement. With inadequate nutritional support or prolonged stress, glutamine levels decrease in both the plasma and the tissue pools, which suggests that glutamine deficiency occurs. This is associated in time with atrophy of the gastrointestinal mucosa. This provision of dietary glutamine results in correction of the abnormally low glutamine concentrations and increased cellularity of the gut mucosa. The derangements in the intestinal mucosa associated with starvation, injury, infection, immunosuppression, chemotherapy, lack of enteral feedings, and other stresses are associated with a breakdown in the barrier function of the gut. Both bacteria and their toxins may enter the host from the intestinal lumen. Through interaction with the reticuloendothelial system, cytokines are produced, which stimulate the pituitary-adrenal axis and thus contribute to the stress response. The elaboration of glucocorticoids facilitates proteolysis, thus increasing glutamine release from skeletal muscle for gut repair. Although this homeostatic mechanism appears to aid mucosal repair and support immunologic responses, severe injury or prolonged glutamine deficits do not adequately support intestinal recovery and allow this cycle to become self-perpetuating (Fig 3). Adequate enteral feedings initiated early in the course of a disease appear to maintain adequate gut barrier function. In the frequent circumstance when feeding by this route is inadequate or impossible, glutamine-containing parenteral feedings offer an appropriate alternative therapy for bowel and immunologic support. Glutamine-containing parenteral feedings are associated with increased mucosal cellularity and improved survival after gut injury. Specific hormones also stimulate mucosal growth, and it is anticipated that a combination of hormones and specific nutrients will provide optimal support of the gut mucosa in the severely ill patient.

Animals↗

PubMed2001

EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption.

Enteropathogenic Escherichia coli (EPEC) alters many functions of the host intestinal epithelia. Inflammation is initiated by activation of nuclear factor (NF)-kappaB, and paracellular permeability is enhanced via a Ca2+- and myosin light-chain kinase (MLCK)-dependent pathway. The aims of this study were to identify signaling pathways by which EPEC triggers inflammation and to determine whether these pathways parallel or diverge from those that alter permeability. EPEC-induced phosphorylation and degradation of the primary inhibitor of NF-kappaB (IkappaBalpha) were tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta independent. In contrast to Salmonella typhimurium, EPEC-stimulated IkappaBalpha degradation and IL-8 expression did not require Ca2+. Instead, extracellular signal-regulated kinase (ERK)-1/2 was significantly and rapidly activated. ERK1/2 inhibitors attenuated IkappaBalpha degradation and IL-8 expression. Although ERK1/2 can activate MLCK, its inhibition had no impact on EPEC disruption of the tight junction barrier. In conclusion, EPEC-induced inflammation 1) is TNF-alpha and IL-1beta receptor independent, 2) utilizes pathways differently from S. typhimurium, 3) requires ERK1/2, and 4) employs signals that are distinct from those that alter permeability. This is the first time that EPEC-activated signaling cascades have been linked to independent functional consequences.

Calcium↗

PubMed2000

Nitric oxide synthase inhibitor ameliorates oral total parenteral nutrition-induced barrier dysfunction.

The expression of inducible nitric oxide synthase (iNOS) is increased in the intestine and results in mucosal damage after endotoxin challenge. Although the oral administration of total parenteral nutrition (TPN) solution promotes bacterial translocation (BT) and increases the intestinal permeability, the role of NO in the nutrition-induced loss of mucosal barrier function remains unclear. The distribution of fluorescein isothiocyanate-dextran (FITC-dextran, 4400) across the lumen of small intestine in rat was examined to investigate the role of NOS activity on the intestinal permeability under oral TPN feeding. Fifty-one rats were randomly divided into 4 groups. Group I (control group) was fed with rat chow, group II received TPN solution orally. Groups III and IV received TPN solution supplemented with NOS inhibitors. On day 9, FITC-dextran was injected into the intestinal lumen. After 30 min, blood samples were taken from portal vein and analyzed for plasma FITC-dextran level by fluorescence spectrophotometry. Samples of small intestine were frozen and sectioned in a cryostat for morphological and NOS histochemical studies. Homogenates of small intestine were used for NOS activity measurement. The plasma level of FITC-dextran showed a significant increase (P < 0.05) in rats fed with oral TPN compared with the control ones. Supplement with NOS inhibitors significantly decreased the intestinal permeability in groups III and IV compared with group II. Similarly, the total NOS activities showed a significant 2-fold increase (P< 0.05) in group II, and NOS inhibitors decreased the elevated NOS activity. These data suggest that oral TPN feeding for 9 days leads to an increase in permeability to dextran and the total NOS activity of small intestine, and both induction of the intestinal permeability and NOS activity were inhibited by treatment with NOS inhibitors. Addition of S-methylisothiourea (SMT), an iNOS selective inhibitor, profoundly inhibited 66% of the induced iNOS activity (P < 0.05) and reduced 74% of the diet-induced increase in intestinal permeability (P < 0.05) in group II. The induced permeability change in rats receiving oral TPN is mainly due to the activity of intestinal mucosal iNOS. The induction of iNOS is an important mediator for intestinal barrier dysfunction. Administration of SMT, which specifically decreases iNOS activity, is useful in the prevention of diet-induced barrier failure.

Administration, Oral↗

PubMed1998

[Pathogenesis of pancreatogenic sepsis].

The intestinal tract is the motor of sepsis in the "gut-MOF hypothesis". Acute pancreatitis causes an early severe reduction of intestinal microcirculation with consequent production of radicals and cytokines damaging intestinal integrity. The intestinal organ dysfunction syndrome results in a breakdown of barrier function and a loss of propulsive activity. This leads to microbial overgrowth and bacterial translocation. This liberates cytokines and causes secondary pancreatic infection after lymphatic and systemic bacterial dissemination. Infected pancreatic necrosis by enteric microorganisms is the main cause of pancreatic sepsis.

Bacterial Translocation↗

PubMed1994

Role of intestinal mucus in transepithelial passage of bacteria across the intact ileum in vitro.

BACKGROUND: Although gastrointestinal mucus is one of a number of putative host defense mechanisms that protect the gut barrier against microbial translocation, little experimental data are available to show its role in this process. The present study sought to determine the role of mucus depletion on the transepithelial passage of bacteria across viable segments of rat ileum mounted in Ussing chambers in vitro. METHODS: Intestinal mucus was depleted in 12 rats after injection with pilocarpine (160 mg/kg intraperitoneally) 45 minutes before intestinal harvest. The mucosal surfaces of the perfused gut segments mounted in the Ussing chamber were exposed to 5 x 10(9) CFU/ml Escherichia coli C-25. Viability was monitored by continuous measurements of the potential difference generated by the membranes. The electrical characteristics were unaltered by pilocarpine pretreatment or exposure to bacteria. RESULTS: Bacterial passage occurred in 100% of pilocarpine membranes as compared with 33.3% in controls (p < 0.05). Pilocarpine-treated membranes resulted in 19.9 +/- 7.5 mg of retrievable mucus as compared with 28.8 +/- 7.2 mg in controls (p < 0.05). Light and transmission electron microscopy revealed an intact epithelial surface in all membranes. There was a marked decrease in mucus on the surface of pilocarpine-treated membranes. CONCLUSIONS: Intestinal mucus secretion is a critical factor in the barrier function of the gut, and its depletion results in a dramatic increase in bacterial passage across the intact rat ileum.

Animals↗

PubMed1998

Escherichia coli cytotoxic necrotizing factor 1 effaces microvilli and decreases transmigration of polymorphonuclear leukocytes in intestinal T84 epithelial cell monolayers.

Cytotoxic necrotizing factor type 1 (CNF1), a 110-kDa toxin-like protein from pathogenic Escherichia coli strains, induces an actin cytoskeleton reorganization consisting of the formation of prominent stress fibers by permanent activation of the small GTP-binding protein Rho. Since p21Rho regulates tight-junction permeability and perijunctional actin reorganization in epithelial intestinal cells (A. Nusrat, M. Giry, J. R. Turner, S. P. Colgan, C. A. Parkos, E. Lemichez, P. Boquet, and J. L. Madara, Proc. Natl. Acad. Sci. USA 92:10629-10633, 1995), we used polarized T84 epithelial intestinal cell monolayers to examine whether CNF1 could affect microvillus structure, transepithelial resistance, and polymorphonuclear leukocyte (PMN) transmigration. Incubation of T84 cells with CNF1 did not influence transepithelial resistance, suggesting that barrier function and surface polarity were not affected by the toxin. However, CNF1 effaced intestinal cell microvilli and induced a strong decrease of PMN transepithelial migration in either the luminal-to-basolateral or the basolateral-to-luminal direction. CNF1 could thus be a virulence factor exhibiting a new type of combined activity consisting of effacing of microvilli and occlusion of the epithelial barrier to PMNs. Attenuated transepithelial migration of PMNs could result in the enhanced growth and protection of luminal bacteria.

Bacterial Toxins↗

PubMed2003

Effects of ethanol on gut-associated lymphoid tissues in a model of bacterial translocation: a possible role of apoptosis.

Chronic ethanol intake has been shown to be associated with immune suppression and impairment of epithelial barrier function. We investigated the effects of ethanol on intestinal immunity and its relation to bacterial translocation (BT). Male Wistar rats were assigned to one of three groups and received respective diets for 28 days. The ethanol-fed group [(EG); n=11] received a liquid diet containing 5% [volume/volume (vol./vol.)] ethanol; a pair-fed group [(PFG); n=11] received an isocaloric diet without ethanol; and a third (control) group [(CG); n=11] received water and chow ad libitum. On experimental day 29, animals in the EG and the PFG underwent distal ileum ligature and small intestine inoculation of a tetracycline-resistant Escherichia coli strain (TcR E. coli R6), by means of gastric intubation, followed by duodenal ligature. One hour after inoculation, mesenteric lymph nodes, right lobe of liver, spleen, and left kidney were excised for bacterial studies. Sections of jejunum and colon were immunostained, with the use of antibodies against immunoglobulin (Ig) A, T cells, macrophages, and proliferating cell nuclear antigen (PCNA). Apoptosis was determined by the terminal deoxynucleotidyltransferase TdT-mediated dUDP-biotin nick end labeling (TUNEL) method. Bacterial translocation rates were greater in the PFG compared with findings for the EG. Lamina propria of the jejunum of the EG showed a reduction in the densities of IgA+ cells and T cells compared with findings for the PFG and the CG. Colonic lamina propria of the EG showed reduced densities of IgA+ cells and macrophages compared with findings for the PFG and the CG. Apoptotic index was increased in the EG compared with findings for the PFG and the CG, in both jejunum and colon. Proliferation index was not significantly different among groups. Results of the current study show that chronic ethanol ingestion led to a reduction of cellular and humoral components of the intestinal mucosa, possibly by cell loss as a result of ethanol-induced apoptosis. The reduced rates of BT observed after chronic ethanol intake seem to indicate that factors irrespective of immune function might be involved in BT inhibition.

Animals↗

PubMed2003

The gesture life of high mobility group box 1.

PURPOSE OF REVIEW: Products of infection, ischemia, and injury stimulate the innate immune system to release proinflammatory cytokines, which act locally to activate specific cellular immune responses and initiate recovery. In pathological cases, however, cytokines are released systemically, resulting in progressive tissue injury, hypotension, organ dysfunction, or death. Observations that animals frequently succumb to systemic inflammation long after the peak activity of tumor necrosis factor and interleukin-1beta suggest that later-acting, downstream inflammatory factors can mediate the pathological sequelae of lethal systemic inflammation. Here, the authors review evidence that the chromosomal protein high mobility group box 1 is a late-acting, downstream mediator of pathological inflammation. RECENT FINDINGS: High mobility group box 1 recently has been identified as a proinflammatory cytokine with significantly delayed release kinetics, as compared with tumor necrosis factor and interleukin-1beta, in animal models of lethal systemic inflammation induced by endotoxin or peritonitis. Administration of exogenous high mobility group box 1 induces acute lung injury, intestinal barrier dysfunction, and lethal systemic inflammatory responses. Its functional cytokine domain has been mapped to the DNA-binding B box, providing structural information that may be useful in the rational design of new therapeutics that target the protein's activity. SUMMARY: Several high mobility group box 1 antagonists have recently been identified. These inhibitors may prove effective in a significantly wider therapeutic window than has been available for previous anti-cytokine strategies, because high mobility group box 1 appears in serum with a significantly delayed kinetics as compared with other cytokines.

Animals↗

PubMed2005

The pivotal role of tumor necrosis factor-alpha in signaling apoptosis in intestinal epithelial cells under shock conditions.

BACKGROUND: Apoptosis is essential for the regulation of cell number and function of intestinal epithelial cells but may contribute to intestinal barrier failure after shock and other low-flow conditions to the gut. METHODS: Caco2 intestinal cell monolayers were challenged with recombinant tumor necrosis factor (TNF). In a second group of experiments, Caco2 cells were exposed to bacteria and/or hypoxia followed by reoxygenation. Apoptosis was detected using annexin-V propidium-iodide staining. Cell culture supernatants were also obtained in the second group of experiments and TNF levels quantitated. Monolayer integrity was assessed by measurement of paracellular permeability and transepithelial electrical resistance. RESULTS: Apical but not basal recombinant TNF increased Caco2 apoptosis. Exposure to either bacteria alone or hypoxia/reoxygenation alone did not increase apoptosis; however, the combined insults significantly increased apoptosis. The increased apoptosis occurred in a delayed fashion in both groups. TNF was released in a polar fashion, and the greatest levels were noted after exposure to both bacteria and hypoxia-reoxygenation. There was also an increase in paracellular permeability in this group; however, no change in transepithelial electrical resistance was noted. The effects on apoptosis and permeability were abrogated by anti-TNF antibodies. CONCLUSION: Intestinal epithelial cell apoptosis contributes to barrier failure after shock conditions and is related to augmented TNF release.

Apoptosis↗

PubMed2004

L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer.

Role of L-glutamine in the protection of intestinal epithelium from acetaldehyde-induced disruption of barrier function was evaluated in Caco-2 cell monolayer. L-Glutamine reduced the acetaldehyde-induced decrease in transepithelilal electrical resistance and increase in permeability to inulin and lipopolysaccharide in a time- and dose-dependent manner; d-glutamine, L-aspargine, L-arginine, L-lysine, or L-alanine produced no significant protection. The glutaminase inhibitor 6-diazo-5-oxo-L-norleucine failed to affect the L-glutamine-mediated protection of barrier function. L-Glutamine reduced the acetaldehyde-induced redistribution of occludin, zonula occludens-1 (ZO-1), E-cadherin, and beta-catenin from the intercellular junctions. Acetaldehyde dissociates occludin, ZO-1, E-cadherin, and beta-catenin from the actin cytoskeleton, and this effect was reduced by L-glutamine. L-Glutamine induced a rapid increase in the tyrosine phosphorylation of EGF receptor, and the protective effect of L-glutamine was prevented by AG1478, the EGF-receptor tyrosine kinase inhibitor. These results indicate that L-glutamine prevents acetaldehyde-induced disruption of the tight junction and increase in the paracellular permeability in Caco-2 cell monolayer by an EGF receptor-dependent mechanism.

Acetaldehyde↗

PubMed1993

[Activity of alkaline phosphatase in the stomach content as a marker of function of gastrointestinal anastomosis after stomach resection].

In 77 patients with gastric ulcer disease, the activity of alkaline phosphatase of gastric juice and its fractions was studied at the late period after resection of the stomach. Activity of thermolabile and thermostable fraction of alkaline phosphatase was the lowest in patients who underwent creation of transverse Billroth-II anastomosis, indicating that it was more physiologic as compared to Hofmeister--Finsterer modification of anastomosis in relation to the barrier (sphincter) function, and thus prevented reflux of the intestinal contents into the stomach.

Adult↗

PubMed1994

[Protein starvation and the trophic barrier functions of the enzymatic and transport systems of the digestive and nondigestive organs in adult and growing rats].

A reduced activity of cytosol dipeptidases was revealed both in epithelial and subepithelial layers of the small intestine against the background of protein deprivation in adult and maturing rats. The latters' enzyme systems of the small intestine and kidneys' layers proved to be particularly sensitive to protein deprivation. The disturbance of the digestive-barrier functions provides favourable conditions for penetration of foreign protein and peptide substances into the organism's inner milieu which can be dangerous for a maturing organism.

Animals↗

PubMedDate not supplied

[The immuno-microbiological characteristics of the small intestine and the translocation of the enteral microflora in acute intestinal obstruction].

The complex examination of 72 patients with acute ileus (AI) of nontumor nature with different severity of endotoxicosis was carried out. The study revealed that AI was accompanied by deep suppression of the immunosecretory and motor evacuatory function of the small intestine, as well as by its pronounced bacterial contamination, mainly due to the significant quantitative prevalence of Gram-negative microflora. The combination of these factors played the key role in the increase of the permeability of the enteric barrier for symbiotic microflora and its massive translocation from the intestinal tract to the internal organs of the body (peritoneal exudate, portal bed), which directly correlated with the severity of endotoxicosis in AI patients. The deficiency of the barrier function of the liver was accompanied by the penetration of infective agents into the general blood stream, thus causing the development of endotoxic shock in AI patients. The analysis of the results thus obtained made it possible to determine the main ways for the elimination of intestinogenic intoxication in AI; they should be aimed at the bacterial decontamination of the small intestine, the restoration of its motor evacuatory and protective barrier functions, the liquidation of portal and systemic bacteremia, the correction of the functional deficiency of the liver.

Acute Disease↗

PubMed2005

Absence of Fer protein tyrosine kinase exacerbates endotoxin induced intestinal epithelial barrier dysfunction in vivo.

BACKGROUND AND AIMS: Fer kinase is activated by a number of growth factors and cytokines, and phosphorylates cortactin during cell shape change induced cortical actin reorganisation. In addition, Fer participates in cytoskeletal interactions mediated by cadherins, platelet endothelial cell adhesion molecule 1 (PECAM-1), and integrins, and has recently been implicated in limiting the innate immune response. Here we examined the role of Fer in modulating leucocyte recruitment and epithelial barrier function in the gut in response to lipopolysaccharide (LPS). METHODS: Mice targeted with a kinase inactivating mutation (FerDR) or strain matched wild-type (129Sv/J) mice were studied after intraperitoneal injection of LPS. Intravital microscopy was used to examine intestinal leucocyte kinetics, and leucocyte infiltration was assessed by fluorescence activated cell sorting. Systemic inflammation was assessed by measuring lung myeloperoxidase activity. Epithelial barrier function was assessed in vivo using blood to lumen 51Cr-EDTA clearance, with or without antibody based depletion of circulating neutrophils. RESULTS: LPS induced a significant increase in leucocyte adhesion and neutrophil infiltration into the intestinal tissue, and increased blood to lumen 51Cr-EDTA clearance. Pretreatment with neutrophil depleting antibody completely abrogated this response in wild-type mice. In FerDR mice, LPS induced leucocyte adhesion within the intestinal venules was exacerbated and associated with a trend towards increased neutrophil transmigration relative to wild-type mice. Surprisingly, LPS induced epithelial barrier permeability was increased 2.5-fold in FerDR mice relative to wild-type mice, and this barrier defect was only partly attenuated by depleting circulating neutrophils by >93 %. CONCLUSIONS: Fer plays a role in regulating LPS induced epithelial barrier dysfunction in vivo through both neutrophil dependent and neutrophil independent mechanisms.

Animals↗

PubMed2001

Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-gamma) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells.

Intestinal epithelial cells seem to play a key role during IBD. The network of cellular interactions between epithelial cells and lamina propria mononuclear cells is still incompletely understood. In the following co-culture model we investigated the influence of intestinal epithelial cells on cytokine expression of T cytotoxic and T helper cells from patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMC) were purified by a Ficoll-Hypaque gradient followed by co-incubation with epithelial cells in multiwell cell culture insert plates in direct contact as well as separated by transwell filters. We used Caco-2 cells as well as freshly isolated colonic epithelia obtained from surgical specimens. Three-colour immunofluorescence flow cytometry was performed after collection, stimulation and staining of PBMC with anti-CD4, anti-CD8, anti-IFN-gamma and anti-IL-4. Patients with IBD (Crohn's disease (CD), n = 12; ulcerative colitis (UC), n = 16) and healthy controls (n = 10) were included in the study. After 24 h of co-incubation with Caco-2 cells we found a significant increase of IFN-gamma-producing CD8+ lymphocytes in patients with IBD. In contrast, healthy controls did not respond to the epithelial stimulus. No significant differences could be found between CD and UC or active and inactive disease. A significant increase of IFN-gamma+/CD8+ lymphocytes in patients with UC was also seen after direct co-incubation with primary cultures of colonic crypt cells. The observed epithelial-lymphocyte interaction seems to be MHC I-restricted. No significant epithelial cell-mediated effects on cytokine expression were detected in the PBMC CD4+ subsets. Patients with IBD-even in an inactive state of disease-exert an increased capacity for IFN-gamma induction in CD8+ lymphocytes mediated by intestinal epithelial cells. This mechanism may be important during chronic intestinal inflammation, as in the case of altered mucosal barrier function epithelial cells may become targets for IFN-gamma-producing CD8+ lymphocytes.

Antibodies, Blocking↗

PubMed2000

[Protective effects of tongli gongxia herbs on gut barrier in rat with multiple organ dysfunction syndrome].

OBJECTIVE: To explore the protective effects of Tongli Gongxia (TLGX) herbs on gut barrier with multiple organ dysfunction syndrome (MODS). METHODS: The MODS models were induced by intraperitoneal injection of Zymosan A, and Dachengqi decoction (DCQD) was used in treating MODS models. The levels of endotoxin in the peripheral and portal blood, and the contents of diamine oxidase (DAO), xanthine oxidase (XOD), malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor (TNF), the permeability of intestinal mucosa and enterocytes, and the histopathologic changes were observed. RESULTS: The gut barrier function in MODS rats were severely damaged. DCQD could significantly reduce the levels of endotoxin in the blood (P < 0.01), the contents of XOD, MDA and TNF in the blood and intestinal tissue were lowered (P < 0.01), but the levels of GSH in blood and intestinal tissue were raised (P < 0.05). Levels of DAO in the intestinal tissue was markedly increased (P < 0.01). DCQD could reduce the permeability of intestinal mucosa and enterocytes, and attenuate the histopathologic changes of intestinal mucosa in MODS rats. CONCLUSION: TLGX herbs have apparently protective effects on the gut barrier in MODS rats.

Amine Oxidase (Copper-Containing)↗