Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giardia lamblia is a ubiquitous parasite that causes diarrhoea. Effective control of Giardia infections in mice has been shown to involve IgA, T cells, mast cells and IL-6. We now show that Tumour necrosis factor alpha (TNFalpha) also plays an important role in the early control of giardiasis. Mice treated with neutralizing anti-TNFalpha antibodies or genetically deficient in TNFalpha were infected with the G. lamblia clone GS/(M)-H7. In both cases, mice lacking TNFalpha had much higher parasite numbers than controls during the first 2 weeks of infections. However, anti-parasite IgA levels, mast cell responses, and IL-4 and IL-6 mRNA levels do not appear significantly altered in the absence of TNFalpha. In addition, we show that mice infected with G. lamblia exhibit increased intestinal permeability, similar to human Giardia infection, and that this increase occurs in both wild-type and TNFalpha deficient mice. We conclude that TNFalpha is essential for host resistance to G. lamblia infection, and that it does not exert its effects through mechanisms previously implicated in control of this parasite.
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PMID:Tumour necrosis factor alpha contributes to protection against Giardia lamblia infection in mice. 1757 66

Bacterium-induced diarrhea results in 2 to 2.5 million deaths in the world each year. The mechanism needs to be further understood. Staphylococcus aureus infection has a close relation with diarrhea; its cell wall component peptidoglycan (PGN) has strong biological activity on immune cells and possibly plays a role in S. aureus-induced diarrhea. The present study showed that oral PGN-induced diarrhea in mice in a dose-dependent manner. Intestinal epithelial cells absorbed PGN via the intracellular pathway. Intestinal mast cells were activated after PGN gavage. Toll-like receptor (TLR)2 expression was detected in mast cells in the intestine as well as in the murine mast cell line p815 cells. Blocking TLR2 or nucleotide-binding oligomerization domain (NOD)1 with related antibodies or RNA interference abolished PGN-induced p815 cell activation. The mast cell mediator histamine and serotonin had synergistic effects in PGN-induced diarrhea. In summary, oral PGN can induce diarrhea in mice, and TLR2 and NOD1 mediate the PGN-induced mast cell activation that plays a critical role in diarrhea induction. Blockade of TLR2 or NOD1 or treating mice with a mast cell stabilizer can efficiently inhibit PGN-induced-diarrhea, providing potential therapeutic significance.
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PMID:Mast cells play a crucial role in Staphylococcus aureus peptidoglycan-induced diarrhea. 1756 75

Sphingosine 1-phosphate (S1P) has been proposed as a regulator of lymphocyte trafficking, but its role in mucosa-associated diseases, such as in food allergies, remains to be elucidated. To examine the role of S1P in allergic diseases in the intestine, we used a Th2 cell-mediated Ag-specific allergic diarrhea model and demonstrated that type 1 S1P receptor (S1P(1)) expression was preferentially associated with pathogenic CD4(+) T cells for the development of allergic reactions. Consistent with this demonstration, treatment with FTY720, a modulator of the S1P(1), prevented allergic diarrhea by inhibiting the migration of systemically primed pathogenic CD4(+) T cells induced by oral challenge with allergen into the large intestine. In addition, FTY720 hampered mast cell infiltration into the large intestine, whereas eosinophil infiltration into the large intestine and total and allergen-specific serum IgE production were comparable between mock- and FTY720-treated groups. These results suggest that modulation of the S1P-mediated pathway to inhibit the migration of pathogenic CD4(+) T cells and mast cells into the large intestine could be a novel strategy for preventing allergic diarrhea.
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PMID:Sphingosine 1-phosphate-mediated trafficking of pathogenic Th2 and mast cells for the control of food allergy. 1764 Oct 24

IL-4Ralpha-mediated STAT6 activation serves an essential role in various animal models of allergy and asthma at both the sensitization and effector phases. IL-4 and IL-13 signaling via the IL-4Ralpha chain exacerbates murine anaphylaxis, but the cell-specific requirements for IL-4Ralpha expression are unclear. The purpose of this study was to elucidate the mechanisms of systemic anaphylaxis to OVA in gene-targeted mice with a deletion of the IL-4Ralpha chain in the macrophage/neutrophil or CD4+ T lymphocyte population. Results demonstrated that anaphylaxis in this model was entirely dependent upon the FcgammaRII/III and was associated with mast cell degranulation. Expression of the IL-4Ralpha on CD4+ T cells, but not macrophages or neutrophils, was critical for severe anaphylaxis, characterized by diarrhea, hypothermia, and death. Ab depletion experiments demonstrated that IFN-gamma protected against mortality and severe intestinal pathology despite the presence of Ag and specific Ab. This protection was associated with reduced levels of mast cell protease, a marker of mast cell degranulation, suggesting that IFN-gamma may inhibit mast cell degranulation in vivo. These data suggest that it may be possible to limit the severity of anaphylaxis using rational therapies designed to increase numbers of IFN-gamma-producing cells by targeting IL-4Ralpha signaling in CD4+ T lymphocytes.
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PMID:CD4+ T cell-specific deletion of IL-4 receptor alpha prevents ovalbumin-induced anaphylaxis by an IFN-gamma-dependent mechanism. 1770 89

Studies with mouse models demonstrate 2 pathways of systemic anaphylaxis: a classic pathway mediated by IgE, FcepsilonRI, mast cells, histamine, and platelet-activating factor (PAF) and an alternative pathway mediated by IgG, FcgammaRIII, macrophages, and PAF. The former pathway requires much less antigen and antibody than the latter. This is modified, however, by IgG antibodies that prevent IgE-mediated anaphylaxis by intercepting antigen before it binds to mast cell-associated IgE. Consequently, IgG antibodies block systemic anaphylaxis induced by small quantities of antigen but mediate systemic anaphylaxis induced by larger quantities. The importance of the alternative pathway in human subjects is unknown, but human IgG, IgG receptors, macrophages, mediators, and mediator receptors have appropriate properties to support this pathway if sufficient IgG and antigen are present. The severity of systemic anaphylaxis is increased by nitric oxide produced by the enzyme endothelial nitric oxide synthase and by the cytokines IL-4 and IL-13 and decreased by endogenous beta-adrenergic stimulation and receptors that contain ITIM that bind tyrosine phosphatases. Anaphylaxis is also suppressed by other receptors and ion channels that function through distinct mechanisms. Unlike systemic anaphylaxis, intestinal anaphylaxis (allergic diarrhea) is almost totally IgE and mast cell dependent and is mediated predominantly by PAF and serotonin. Some potent food allergens, including peanuts and tree nuts, can directly enhance anaphylaxis by stimulating an anaphylactoid response through the innate immune system. Results of these studies suggest novel prophylactic agents, including nonstimulatory anti-IgE mAbs, IL-4 receptor antagonists, PAF antagonists, and agents that cross-link FcepsilonRI or FcgammaRIII to an ITIM-containing inhibitory receptor.
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PMID:Anaphylaxis: lessons from mouse models. 1776 51

A localized Th2 milieu has been observed in the intestine of subjects with food allergic disorders; however, the role of T cells in the pathophysiology of these disorders remains poorly understood. Our aim was to examine sites of T cell activation in response to food challenge, identify potential factors responsible for T cell recruitment to the gut, and determine the role of T cells in disease. BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly fed with OVA to induce allergic diarrhea. Local cytokine and chemokine expressions were assessed by quantitative PCR, and cytokine secretion levels in the mesenteric lymph node (MLN) were determined by ELISA. Homing molecule expression was determined by flow cytometry, and the role of CD4(+) T cells in promoting disease was tested by adoptive transfer. Mice developed diarrhea associated with changes in epithelial ion transport, mast cell infiltration, intestinal IgE secretion, and local upregulation of Th2 cytokines and the Th2 chemokines CCL1, CCL17, and CCL22 in the small intestine. T cell activation occurred in the MLN before symptom onset, and a single feed of OVA induced T cell proliferation, alpha(4)beta(7) upregulation, and CD62L downregulation. Cells from the MLN, including purified CD4(+) T cells, were able to transfer allergic diarrhea to naive mice. A gut-homing phenotype induced in the MLN and selective upregulation of Th2 chemoattractants are likely important factors in the gastrointestinal recruitment of pathological Th2-skewed CD4(+) T cells in food allergy.
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PMID:CD4 T cells activated in the mesenteric lymph node mediate gastrointestinal food allergy in mice. 1791 45

The efficacy of electroacupuncture (EA) for treating patients with diarrhea-predominant IBS has been confirmed in the authors' former research, but the regulatory mechanism of EA in IBS is still unknown. The aim of this study was to explore the relationship between the effect of EA on treating IBS rats and the activation and proliferation of mast cell (MC), the secretion of substance P(SP), and vasoactive intestinal polypeptide (VIP). The IBS rat model was set up with stress of binding limbs and colorectal distention. All rats were randomly assigned to four groups (Normal, Model, Tegaserod and EA). Hematoxylin and eosin staining has been used to observe the pathological change in the rats' colonic mucosa and an AWR scoring system has been applied to evaluate improvement of visceral hypersensitivity in various methods of the different groups. Toluidine blue improved method (TBI) and immunohistochemistry have also been involved in observations of mucous mast cells in the colon, change of c-fos positive cells, and secretion of SP, SPR, VIP, VIPR in the local colon. Firstly, the threshold of visceral sensitivity in the rats model with IBS was remarkably reduced (P < 0.01). The MC count in colonic mucosa and c-fos positive cells count increased significantly (P < 0.01) with positive correlation within each. Secondly, EA on ST-25 and Tegaserod pouring into the stomach can inhibit the proliferation and activation of MC in the colon and regulate secretion of SP, SPR, VIP, VIPR (P < 0.01, P < 0.05), while the effect of EA is obviously superior to Tegaserod. We concluded, firstly, that the abnormal proliferation and activation of mucous mast cells in the colon, and oversecretion of neuropeptides such as SP, VIP and their receptors could be one of key mechanisms of etiology of IBS. Secondly, the inhibition of activation and proliferation and the secretion of SP, VIP could be major effects of EA when treating rats with IBS.
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PMID:Regulatory mechanism of electroacupuncture in irritable bowel syndrome: preventing MC activation and decreasing SP VIP secretion. 1799 87

Soybean allergy represents a significant health threat to individuals with food allergies. Glycinin, the main storage protein in soybean, has been identified as a major food allergen. The present study was conducted to investigate the mechanism of glycinin-induced hypersensitivity in a swine model. The relationship between glycinin dose and the severity of hypersensitive reactions was also explored. Twenty-four piglets weaned at 18 days were gastric sensitized and subjected to repeated oral challenges with diets containing 0%, 2%, 4% and 8% glycinin. The results showed that dietary supplementation of glycinin reduced piglet performance (P<.01) while increasing occurrence of diarrhea (P<.05) and erythema area (P=.01) in response to an intradermal injection of glycinin. Intestinal mast cell numbers (P<.05) and immunoglobulin E (IgE) levels (P<.05) were increased linearly, whereas the histamine content in intestinal specimens (except in the duodenum) was decreased (P<.01), indicating that more histamine had been released in glycinin-fed piglets than in control. Serum concentrations of total IgE, glycinin-specific IgG1 and interleukin (IL)-4 and IL-10 were also greater (P<.05) in the pigs treated with glycinin. In this study, we found that glycinin-induced hypersensitivity is a predominantly Th2-type immune response, mediated by IgE and associated with increases in intestinal mast cell numbers and histamine release as well as IL-4 and IL-10 concentrations in the serum of sensitized piglets, resulting in diarrhea and reduced performance. The severity of the hypersensitive reactions depends on the dose of glycinin. Higher dose may cause more severe anaphylactic symptoms.
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PMID:Effects of glycinin on IgE-mediated increase of mast cell numbers and histamine release in the small intestine. 1828 Jan 35

The present study was designed to investigate the antidiarrhoeal potential of 50% ethanolic extract of Cinnamomum tamala on experimentally induced castor oil diarrhoea, gastric emptying of phenol red meal, gastrointestinal transit of charcoal meal and in vitro mast cell degranulation activity. C. tamala extract (25, 50 and 100 mg/kg, orally) produced a dose-dependent reduction in the total amount of faecal matter in castor oil-induced diarrhoea. The mean distance travelled by charcoal meal at 50 and 100 mg/kg of extract showed a significant reduction in the secretion of gastrointestinal fluid accumulation by 32.5-65.0%. The Na(+) and K(+) concentrations on castor oil-induced fluid accumulation showed a greater inhibitory effect on Na(+) levels than on K(+) concentrations. C. tamala significantly reduced the lipid peroxidation (P < 0.001) and increased the catalase (P < 0.01) activity in comparison to the castor oil-induced groups. C. tamala leaf extract did not show any significant effect at a higher dose (15 mg/ml) on mast cell degranulation. However, the extract in the dose of 5 and 10 mg/ml conferred significant mast cell protective action (P < 0.001). The percentage of eugenol in extract is 3.8% w/w, and total tannin is 247.5 mg/g. The result indicates the Indian spice C. tamala is useful for diarrhoea.
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PMID:Antidiarrhoeal activity of the standardised extract of Cinnamomum tamala in experimental rats. 1849 39

Systemic mastocytosis is an uncommon condition characterized by abnormal proliferation of mast cells in one or more organ. The specific D816V KIT mutation is present in most cases. Gastrointestinal symptoms occur commonly but histologic characterization of gastrointestinal involvement is incomplete. The purpose of this study was (1) to describe the clinicopathologic features in five patients with systemic mastocytosis involving the gastrointestinal tract and (2) to determine whether gastrointestinal involvement is associated with the usual D816V mutation or a different mutation. Clinical details were obtained from the hospital of origin or referring pathologist. Histologic features were documented in slides stained with hematoxylin and eosin, mast cell tryptase and CD117. Molecular analysis for the D816V KIT mutation was performed on formalin-fixed paraffin-embedded sections. Symptoms included diarrhea/loose stools (n=5), abdominal pain (n=4), vomiting (n=3) and weight loss (n=3). Other findings included cutaneous lesions of mastocytosis (n=4), malabsorption (n=2), hypoalbuminemia (n=2) and constitutional growth delay (n=1). Sites of gastrointestinal involvement included the colon (n=5), duodenum (n=3) and terminal ileum (n=3). Endoscopic/gross findings included mucosal nodularity (n=4), erosions (n=2) and loss of mucosal folds (n=2). In three patients the endoscopic appearance was considered consistent with inflammatory bowel disease. All cases showed increased mast cell infiltration of the lamina propria, confirmed by immunohistochemistry for mast cell tryptase and CD117. In two cases, mast cells had abundant clear cytoplasmic resembling histiocytes. Marked eosinophil infiltrates were present in four patients, in one patient leading to confusion with eosinophilic colitis. Architectural distortion was noted in three cases. The D816V KIT mutation was present in all four cases tested. In conclusion, gastrointestinal involvement by systemic mastocytosis is characterized by a spectrum of morphologic features that can be mistaken for inflammatory bowel disease, eosinophilic colitis or histiocytic infiltrates. Systemic mastocytosis involving the gastrointestinal tract is associated with the usual D816V KIT mutation.
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PMID:Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases. 1893 52


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