ovalbumin and Enteritis

Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Antioxidants; Cell Degranulation; Colitis; Enteritis; Hypersensitivity; Interleukin-10; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Resveratrol

Eosinophils are the main inflammatory effector cells that damage gastrointestinal tissue in eosinophilic gastrointestinal diseases (EGIDs). Activation of the OX40 pathway aggravates allergic diseases, such as asthma, but it is not clear whether OX40 is expressed in eosinophils to regulate inflammation in EGIDs. In this study, we assessed the expression and effect of OX40 on eosinophils in WT and. Eosinophil infiltration, ovalbumin (OVA)-specific Ig production, OX40 expression and inflammatory factor levels in the intestine and bone marrow (BM) were investigated to evaluate inflammation.

Topics: Animals; Enteritis; Eosinophilia; Eosinophils; Gastritis; Inflammation; Mice; NF-kappa B; Ovalbumin; Receptors, OX40; RNA, Messenger; TNF Receptor-Associated Factor 2

Aberrant accumulation and activation of eosinophils and potentially mast cells (MCs) contribute to the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), including eosinophilic esophagitis (EoE), gastritis (EG), and gastroenteritis (EGE). Current treatment options, such as diet restriction and corticosteroids, have limited efficacy and are often inappropriate for chronic use. One promising new approach is to deplete eosinophils and inhibit MCs with a monoclonal antibody (mAb) against sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8), an inhibitory receptor selectively expressed on MCs and eosinophils. Here, we characterize MCs and eosinophils from human EG and EoE biopsies using flow cytometry and evaluate the effects of an anti-Siglec-8 mAb using a potentially novel Siglec-8-transgenic mouse model in which EG/EGE was induced by ovalbumin sensitization and intragastric challenge. MCs and eosinophils were significantly increased and activated in human EG and EoE biopsies compared with healthy controls. Similar observations were made in EG/EGE mice. In Siglec-8-transgenic mice, anti-Siglec-8 mAb administration significantly reduced eosinophils and MCs in the stomach, small intestine, and mesenteric lymph nodes and decreased levels of inflammatory mediators. In summary, these findings suggest a role for both MCs and eosinophils in EGID pathogenesis and support the evaluation of anti-Siglec-8 as a therapeutic approach that targets both eosinophils and MCs.

Topics: Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Disease Models, Animal; Enteritis; Eosinophilia; Eosinophilic Esophagitis; Eosinophils; Female; Gastritis; Gastroenteritis; Humans; Lectins; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin

The aim of this study was to further explore the possible mechanisms of montelukast on oral mice ovalbumin-induced eosinophilic gastroenteritis in a mouse model. The results indicated that montelukast could prevent levels of eotaxin-1 and interleukin-5 in intestinal mucosa homogenate when compared with model group. Interestingly, the increase of major basic protein expression in jejunal tissue also was attenuated by treated with montelukast.

Topics: Acetates; Animals; Chemokine CCL11; Cyclopropanes; Enteritis; Eosinophil Major Basic Protein; Eosinophilia; Gastritis; Gene Expression Regulation; Interleukin-5; Leukotriene Antagonists; Mice; Mice, Inbred BALB C; Ovalbumin; Quinolines; Sulfides

Gastrointestinal eosinophilic (EG) is a rare and heterogeneous condition characterized by patchy or diffuse eosinophilic infiltration of gastrointestinal tissue. Pharmacological study so far has demonstrated that montelukast, an oral leukotriene receptor antagonist, might be considered in patients with this disease. The aim of this study was to evaluate the effect of montelukast on oral ovalbumin (OVA) allergen induced EG inflammation in mice and to suggest some mechanisms underlying this effect. Twenty-four mice were divided into three experimental groups: PBS control, OVA group, and montelukast treated group. The mice were sensitized intraperitoneally and challenged intragastrically with OVA, and were treated with montelukast. Gastrointestinal symptoms were observed after challenged intragastrically with OVA. Eosinophils count in blood, serum OVA specific IgE and gastrointestinal histology were evaluated. Montelukast could significantly reduce the severity of oral allergen-induced eosinophilic inflammation, villous atrophy, and associated symptoms of weight loss associated with diarrhea. Montelukast also could ameliorate OVA-induced gastrointestinal pathological lesions, which was associated with the decrease of IgE and LTD4 levels, and this might be one of the important mechanisms of montelukast that protected gastrointestinal injury from EG. These findings indicated that montelukast therapy may be a novel therapeutic approach for EG and other eosinophil-mediated diseases.

Topics: Acetates; Animals; Body Weight; Cyclopropanes; Enteritis; Eosinophilia; Eosinophils; Female; Gastric Mucosa; Gastritis; Gastroenteritis; Immunoglobulin E; Inflammation; Jejunum; Leukotriene D4; Mice; Mice, Inbred BALB C; Ovalbumin; Quinolines; Stomach; Sulfides

Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen-related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell-mediated inflammation in the intestine.. Expression of IFN-λ and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell-mediated intestinal inflammation was used to examine the role of IFN-λ and T cells in oral tolerance in the intestine.. CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-λ-primed CD3+ cells inhibited Th2 cell-mediated inflammation in the intestine.. IFN-λ is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell-mediated inflammation in patients.

Topics: Animals; Apoptosis; Blotting, Western; CD3 Complex; Cells, Cultured; Cytokines; Dendritic Cells; Disease Models, Animal; Enteritis; Flow Cytometry; Genes, T-Cell Receptor; Immune Tolerance; Immunity, Mucosal; Immunohistochemistry; Intestines; Mice; Mice, Inbred BALB C; Mice, Transgenic; Mouth Mucosa; Ovalbumin; Phagocytosis; Receptors, Cytokine; Th2 Cells

The B7 family member programmed death-1 ligand (PD-L1) has been shown to play an inhibitory role in the regulation of T cell responses in several organs. However, the role of PD-L1 in regulating tolerance to self-Ags of the small intestine has not been previously addressed. In this study, we investigated the role of PD-L1 in CD8(+) T cell tolerance to an intestinal epithelium-specific Ag using the iFABP-tOVA transgenic mouse model, in which OVA is expressed as a self-Ag throughout the small intestine. Using adoptive transfer of naive OVA-specific CD8(+) T cells, we show that loss of PD-1:PD-L1 signaling, by either Ab-mediated PD-L1 blockade or transfer of PD-1(-/-) T cells, leads to considerable expansion of OVA-specific CD8(+) T cells and their differentiation into effector cells capable of producing proinflammatory cytokines. A fatal CD8(+) T cell-mediated inflammatory response develops rapidly against the small bowel causing destruction of the epithelial barrier, severe blunting of intestinal villi, and recruitment and activation of myeloid cells. This response is highly specific because immune destruction selectively targets the small intestine but not other organs. Collectively, these results indicate that loss of the PD-1:PD-L1 inhibitory pathway breaks CD8(+) T cell tolerance to intestinal self-Ag, thus leading to severe enteric autoimmunity.

Topics: Adoptive Transfer; Animals; Antigens, Surface; Apoptosis Regulatory Proteins; Autoantigens; Autoimmune Diseases; B7-1 Antigen; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Cell Differentiation; Enteritis; Flow Cytometry; Immune Tolerance; Immunity, Mucosal; Intestines; Lymphocyte Activation; Membrane Glycoproteins; Mice; Mice, Transgenic; Ovalbumin; Peptides; Programmed Cell Death 1 Receptor

The immunoregulatory properties of primary colonic epithelial cells (CECs) have not been defined. The ability of CECs from wild-type and interleukin 2-deficient (IL-2(-/-)) mice to take up a complex protein antigen and present peptides via MHC molecules to T cells was assessed and contrasted with that of primary small intestinal epithelial cells (SIECs).. Uptake of fluorescein isothiocyanate (FITC)-labeled ovalbumin (FITC-OVA) by CECs and SIECs from wild-type and IL-2(-/-) mice was measured by flow cytometry. The effect of disrupting cytoskeleton organization and metabolic activity of CEC on antigen uptake was assessed. An OVA/I-A(b)-specific CD4(+) T-cell line transfected with an NFAT-lacZ reporter gene construct was used to evaluate the ability of CECs and SIECs as well as CECs from healthy and colitic IL-2(-/-) mice to present antigen to T cells.. Uptake of FITC-OVA by CECs is concentration dependent, is not saturated at physiologic concentrations, and requires metabolically active cells. CECs from IL-2(-/-) mice take up significantly more antigen than those from wild-type mice. CECs are more efficient APCs than SIECs, and antigen-pulsed CECs from IL-2(-/-) mice induce the highest levels of T-cell activation.. Primary CECs are efficient APCs for CD4 MHC class II-restricted T cells. Antigen uptake and presentation is up-regulated in animals prone to develop intestinal inflammation.

Topics: Animals; Antigen-Presenting Cells; Antigens; CD4-Positive T-Lymphocytes; Cell Line; Colitis; Colon; Enteritis; Female; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Interleukin-2; Intestinal Mucosa; Intestine, Small; Mice; Mice, Inbred C57BL; Ovalbumin; Reference Values

For many years the central focus of research into gastrointestinal hypersensitivity reactions has been the mast cell population of the intestinal lamina propria. Since bile is known to deliver immunological mediators to the gastrointestinal tract, the possibility arises that extra-intestinal populations of mast cells may also contribute to IgE-mediated intestinal damage.. To characterize hepatic mast cells in the rat and to investigate the role of the hepatobiliary system in a model of IgE-mediated reactivity to dietary antigen.. Wistar rats were passively sensitized with monoclonal antidinitrophenyl (DNP) IgE antibodies, and were later challenged orogastrically with DNP-HSA. Additional animals were sensitized, then bile duct-cannulated prior to antigen challenge. At various time points, liver and intestinal samples were collected for histological examination, and bile was collected and assayed for histamine and TNFalpha.. Hepatic mast cells display a mucosal mast cell-like phenotype, and are closely associated with the vessels of the portal triads. Orogastric antigen challenge led to a rapid and significant decline (P<0.0001) in detectable mast cells as a result of anaphylactic degranulation. The median number of granulated mast cells associated with each portal triad in liver sections declined from six per portal triad to one per portal triad post-antigen challenge. After 15 min, biliary histamine concentrations rose above background levels (P<0.01). TNFalpha was also detectable in the majority (4/6) of bile samples within 15 min of challenge. Histological examination of the gastrointestinal mucosa revealed disruption to the villous epithelium ranging from oedematous changes to gross destruction. Such damage was not seen in animals in which bile had been externally drained.. The data indicate that biliary products are major contributors to the gastrointestinal damage arising from IgE-mediated hypersensitivity reactions in the rat, and such hypersensitivity reactions may involve a population of mast cells which reside in the liver.

Topics: Animals; Bile; Biliary Tract; Blotting, Western; Cell Count; Dinitrophenols; Enteritis; Food Hypersensitivity; Histamine; Immunoglobulin E; Liver; Mast Cells; Ovalbumin; Radioimmunoassay; Rats; Rats, Wistar; Serum Albumin; Tumor Necrosis Factor-alpha

The oral administration of non-steroidal anti-inflammatory drugs (NSAID) to animals induces a quick increase in intestinal permeability and secondary inflammatory lesions of the intestine. The mechanisms leading to the inflammatory lesions are hypothetical. The increased intestinal permeability could allow a greater mucosal and systemic penetration of fed antigens and bacterial products leading to an abnormal mucosal and systemic immune and inflammatory response toward these materials. We examined the effect of oral dosing with indomethacin on ovalbumin serum levels and the systemic immune response to ovalbumin in mice fed with ovalbumin. The ovalbumin serum level was higher in indomethacin-treated mice and the increase was proportional to the dose of indomethacin. It was associated with epithelial and subepithelial lesions. Moreover, the systemic humoral and, to a lesser extent, the cellular tolerance were partially abrogated in the treated mice. These findings suggest that the oral administration of indomethacin in mice induces an increased passage of fed antigen through the intestinal epithelium associated with a decrease in systemic tolerance to this antigen. The reason for this decrease remains unclear. Besides a disequilibrium between systemic and mucosal immune responses, a loss of integrity of the intestinal epithelial cells and a direct immunomodulating effect of indomethacin may also be involved. This decrease in systemic tolerance to luminal antigen could be involved in the development of NSAID enteropathy.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies; Enteritis; Female; Hypersensitivity, Delayed; Ileum; Immune Tolerance; Indomethacin; Injections, Subcutaneous; Intestinal Mucosa; Jejunum; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred BALB C; Ovalbumin; Permeability

Conclusive evidence of particular aetiologic factors in human inflammatory bowel diseases (IBDs) has not been obtained. However, there is information to suggest that immunologic mechanisms are involved in the pathogenesis and perpetuation of both ulcerative colitis and Crohn's disease. A TNBS-induced enteritis was developed by immunisation and local challenge of rats with TNBS. This animal model mimicked several features of human Crohn's disease. Because of the immunoglobulin component in human Crohn's disease, investigation of the TNBS-induced immunological response in the animal model was performed. A specific ELISA was developed to assess the humoral part of the TNBS sensitisation in the rat. Investigation of sera obtained from sensitized animals 11 weeks after the start of TNBS immunisation procedure revealed a clear IgG-specific immune response against TNBS. Immunoglobulin subtypes were differentiated by goat anti-rat antibodies and results indicate a specific IgG2 subtype response.

Topics: Animals; Enteritis; Immunoglobulin G; Ovalbumin; Rats; Trinitrobenzenesulfonic Acid

Investigations into the role of allergic enteropathy in acute and chronic intestinal inflammation have been hampered by the lack of objective confirmation for intestinal mast cell activation. Utilizing an established model of acute allergic enteropathy in the rat, we report the enhanced intraluminal recovery of the mast cell mediator histamine after in vivo antigen challenge in sensitized animals. The enhanced histamine recovery is dose dependent, antigen-specific, and restricted to that segment of bowel challenged, thus confirming local intestinal anaphylaxis. The progression of histologic enteropathy is documented and shown to correlate with the entry of mast cells into the intestinal lumen during, but not before, the anaphylactic response. Pretreatment of the sensitized animal with prostaglandin E2 or doxantrazole, but not cromolyn, significantly inhibits the anaphylactic response.

Topics: Acute Disease; Adjuvants, Immunologic; Anaphylaxis; Animals; Dinoprostone; Enteritis; Female; Histamine; Histamine Release; History, Ancient; Hookworm Infections; Immunization; Nippostrongylus; Ovalbumin; Prostaglandins E; Rats; Rats, Inbred Strains; Thioxanthenes; Xanthones

An intestinal immunisation procedure involving systemic priming and oral boosting was investigated in lambs with a view to providing vaccination control of enteritis in young animals. The procedure stimulated the appearance of antibody-containing cells of IgA specificity in the intestine and lambs immunised in this way with a bacterial vaccine were protected against subsequent challenge with live enteropathogenic bacteria. This immunisation regime therefore provides a useful method for the stimulation of IgA immunity in the intestine of ruminants and it is anticipated that it will have general application to a variety of enteric diseases.

Topics: Animals; Antibodies, Bacterial; Bacterial Infections; Enteritis; Female; Immunization; Immunization Schedule; Models, Biological; Ovalbumin; Salmonella Infections, Animal; Salmonella typhimurium; Sheep; Sheep Diseases