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)

Clinical evidence suggests that idiosyncratic hepatitis following administration of halogenated volatile anesthetics is mediated by autoimmune responses. No murine model to study mechanisms of anesthetic-induced or any other form of drug-induced idiosyncratic hepatitis exists. Anesthetics are believed to trigger hepatitis by covalently linking a trifluoroacetyl (TFA) chloride hapten to hepatic proteins, forming haptenated self-proteins. To test this hypothesis, we developed a hapten-induced model of hepatitis by immunization with syngeneic S100 liver proteins covalently coupled to TFA (TFA-S100). We found that TFA-S100 induced hepatitis was more severe than disease induced by S100 plus adjuvants or by the adjuvant alone and was characterized by neutrophil, mast cell, and eosinophil infiltration. TFA-specific IgG1 antibodies directly correlated with hepatitis, whereas S100 autoantibodies did not. TNF-alpha, IL-1beta, and IL-6 released from splenocytes collected 2 weeks after TFA-S100 inoculation were increased resembling the elevated serum cytokines reported in patients with autoimmune hepatitis (AIH). Three weeks after inoculation, the peak of hepatitis, we noted decreased numbers of Kupffer cells and lower levels of IL-6 and IL-10 in the liver, cytokines produced by Kupffer cells. This is the first report, to our knowledge, of a hapten-induced model of hepatitis with immune and autoimmune features.
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PMID:A novel model of drug hapten-induced hepatitis with increased mast cells in the BALB/c mouse. 1571 33

While probing host skin to search for blood vessels, the female Anopheles mosquito delivers Plasmodium parasites in the presence of saliva. Saliva from various blood-feeding vectors which contains several pharmacologically active components is believed to facilitate blood feeding as well as parasite transmission to the host. Recently, we found that mosquito saliva has the capacity to activate dermal mast cells and to induce local inflammatory cell influx. Our main objective in the present work is to investigate whether saliva, through mosquito bites, controls the magnitude of Ag-specific immune responses and whether this control is dependent on the mast cell-mediated inflammatory response. Using a mast cell knockin mouse model, we found that mosquito bites consistently induced MIP-2 in the skin and IL-10 in draining lymph nodes, and down-regulate Ag-specific T cell responses by a mechanism dependent on mast cells and mediated by IL-10. Our results provide evidence for new mechanisms which may operate during Plasmodium parasite transmission by mosquito bites.
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PMID:Mast cell-dependent down-regulation of antigen-specific immune responses by mosquito bites. 1654 50

Early nutritional events have the potential to affect health outcomes in later life including the development of allergy. Food allergy is usually the first manifestation of allergy. Breast-feeding has been associated with a protective effect against the development of allergy, but the evidence is contradictory and the mechanisms involved are not clear. We hypothesize that milk cytokines, such as transforming growth factor beta (TGF-beta), play a role in regulating immune responses to dietary antigens. Using a rat pup model of gastrostomy feeding, the immune response profile, at weaning and post-weaning, of allergy-prone Brown Norway rats fed formula supplementation with TGF-beta was assessed. We show that feeding formula to allergy-prone rat pups results in increased total IgE immunoglobulin, beta-lactoglobulin (BLG) IgG1 antibody, and mucosal mast cell activation, as measured by serum rat mast cell protease II (RMCPII) levels in the gut. Supplementation of formula with physiological levels of TGF-beta down-regulated the BLG IgG1 response as well as total IgE and mucosal mast cell activation. Supplementation of formula also resulted in an increase in Th1 cytokines, interleukin (IL)-18, IL-12p40, IL-12p35, and interferon gamma (IFN-gamma) and an increase in IL-10. In conclusion, TGF-beta supplementation of formula moved the immune response profile of allergy prone (Th2 type) rat pups toward a Th1 profile in the suckling period. Importantly, this immune profile persisted after weaning when TGF-beta was no longer present in the diet.
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PMID:Effects of transforming growth factor-beta and formula feeding on systemic immune responses to dietary beta-lactoglobulin in allergy-prone rats. 1662 76

In order to investigate immunological changes over time in pigs infected with Trichuris suis, we inoculated 40 pigs with 5000 infective T. suis eggs and left 40 pigs as uninfected controls. Equal numbers of pigs from both groups were sacrificed every other week from 1 to 11 weeks p.i. At necropsy tissue samples were collected from all pigs and their worm burdens were determined. In the proximal colon of T. suis-infected pigs infiltration of eosinophils peaked 5 weeks p.i. and mast cell infiltration developed from 5 to 11 weeks p.i. Histological evaluation of the proximal colon revealed that the presence of T. suis was closely associated with intestinal histopathological changes such as crypt hyperplasia, goblet cell hyperplasia and a general hypertrophy of mucosa. The crypt lengths were positively associated with worm burdens. Real-time PCR analysis of genes related to immune function indicate a local increased transcription of genes coding for CCR3, ARG1, MUC5AC, IL-4, IL-5, IL-13, FcepsilonR1alpha, and IL-13Ralpha2 and decreased expression of genes coding for iNOS, TNF-alpha, IL-10, CD3epsilon, CD80, CD86, IL-4Ralpha, IL-13Ralpha1 and CD40 in the proximal colon of pigs infected with T. suis. This local T-helper cell Type 2-like gene-expression pattern indicates that the Type 2 immune response characteristic of helminth infections in both mouse and humans also develops in pigs infected with T. suis. The results from this study expand our knowledge of the immunomodulatory effect of T. suis, a parasite that has proven effective in treating inflammatory bowel disease, when its eggs are administered regularly to patients.
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PMID:A time course study of immunological responses in Trichuris suis infected pigs demonstrates induction of a local type 2 response associated with worm burden. 1675 May 34

Interleukin (IL)-10 is a potent immunoregulatory cytokine capable of inhibiting the inflammatory response. As mast cells and macrophages are central effectors of inflammation, we investigated the effects of IL-10 on mast cell and macrophage development from mouse bone marrow progenitors. Bone marrow cells were cultured in IL-3 + stem cell factor (SCF), giving rise to mixed populations of mast cells and macrophages. The addition of IL-10 greatly decreased the expansion of bone marrow progenitor cells through a mechanism requiring signal tranducer and activator of transcription-3 expression. The inhibitory effects were a result of the induction of apoptosis, which occurred with caspase-3 activation and reduced mitochondrial membrane potential. Supporting a role for the mitochondrion, bone marrow cells from p53-deficient or Bcl-2 transgenic mice were partly resistant to the effects of IL-10. Further, IL-10 decreased Kit receptor expression and inhibited survival signaling by SCF or IL-3. These data indicate that IL-10 induces an intrinsic, mitochondrial apoptosis cascade in developing mast cells and macrophages through mechanisms involving blockade of growth factor receptor function. The ability of IL-10 to inhibit survival could support immune homeostasis by dampening inflammatory responses and preventing chronic inflammation.
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PMID:Interleukin-10 induces apoptosis in developing mast cells and macrophages. 1682 33

Recent studies have demonstrated that mast cells not only mediate inflammatory reactions in type I allergy but also play an important role in adaptive immunity. In the present study, we investigated the effects of interferon-alpha, which shares the same receptor as IFN-beta, on human cord blood-derived mast cells. Mast cells produced TNF-alpha, and IL-10, and expressed OX40 ligand upon activation by crosslinking of FcepsilonRI. When treated with interferon-alpha, TNF-alpha production was decreased while IL-10 and TGF-beta productions were increased. Furthermore, flow cytometric analysis revealed that interferon-alpha downregulated expression OX40 ligand on mast cells which is crucial for mast cell-T cell interaction. We confirmed that the viability of mast cells was not affected by interferon-alpha treatment. Accordingly, interferon-alpha-treated mast cells induced lower levels of CD4+ T cell proliferation compared with those without interferon-alpha treatment. These results suggest that type I interferons suppress T cell immune responses through their regulatory effects on mast cells.
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PMID:Type I interferons attenuate T cell activating functions of human mast cells by decreasing TNF-alpha production and OX40 ligand expression while increasing IL-10 production. 1698 87

Disorders involving mast cells are extremely common in dogs, ranging from allergic diseases to neoplastic transformation resulting in malignant mast cell tumors. Relatively little is known regarding the basic biologic properties of normal canine mast cells, largely due to the difficulty in reliably purifying large numbers from canine skin. In vitro generated bone marrow derived cultured mast cells (BMCMCs) are routinely used in both human and murine studies as a ready source of material for in vitro and in vivo studies. We previously developed a technique to generate canine BMCMCs from bone marrow derived CD34+ cells and demonstrated that these cells exhibit the phenotypic properties characteristic of mast cells and release histamine in response to IgE cross-linking. The purpose of the following study was to characterize the functional properties of these canine BMCMCs and contrast these with the functional properties of murine BMCMCs. Our work demonstrates that both IL-4 and IL-10 promote canine BMCMC proliferation, possibly through upregulation of Kit expression, while TGFbeta inhibits proliferation. The canine BMCMCs produce a variety of cytokines and chemokines in response to IgE cross-linking and chemical stimulation including IL-3, IL-4, IL-13, GM-CSF, RANTES, and MIP1alpha. Interestingly, the canine BMCMCs released significantly larger amounts of MCP-1 and tryptase and significantly smaller amounts of IL-6 following chemical stimulation and IgE cross-linking when compared to murine BMCMCs. Lastly, the canine BMCMCs produced larger amounts of active MMP9 than their murine counterparts. In summary, canine BMCMCs exhibit unique functional properties that distinguish them from murine BMCMCs and provide insight into the contribution of these cells to mast cell disorders in the dog.
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PMID:A functional comparison of canine and murine bone marrow derived cultured mast cells. 1702 94

Interleukin 9 (IL-9) is a T-cell derived factor preferentially expressed by CD4+ Th2 cells and it has been characterized both in human and murine systems. It is a pleiotropic cytokine with multiple functions on cells of the lymphoid, myeloid and mast cell lineages, as well as on lung epithelial cells. Other activities described for IL-9 support its contribution to asthma and its important role in helminthic infections, where a Th2 response can be protective and IL-9 enhances resistance or is responsible for elimination of the nematode. Nevertheless, until recently there were no studies on its role in bacterial infections in man. We have demonstrated that cytokines can modulate the specific cytotoxicity generation in peripheral blood mononuclear cells from leprosy patients and normal controls. In the present report we studied the effect of IL-9 in this experimental model. Our results indicate that IL-9 can counteract the negative effect mediated by IL-4 on the generation of M. leprae-induced cytotoxic T lymphocytes. Moreover, it can increase this lytic activity in controls and enhance the stimulatory effect of IL-2 or IL-6 in cells from leprosy patients and controls. IL-9 is also able to revert the inhibitory effect of IL-10 and IL-13 on the M. leprae-induced cytotoxic activity. Although the exact mechanism of action of IL-9 remains to be determined, interferon gamma seems to be required for the effect of IL-9 in this experimental model. These data suggest that IL-9 may have an atypical Th2 behaviour and play a role in the modulation of the immune response to mycobacterial infections.
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PMID:IL-9 promotes anti-Mycobacterium leprae cytotoxicity: involvement of IFNgamma. 1717 73

Mast cells are well known for their role in allergic disease and have recently been implicated in inflammatory disorders, including autoimmune arthritis, multiple sclerosis, and atherosclerosis. Although aberrant mast cell activation is the focus of many studies, much less is known about normal mast cell homeostasis. Because loss of the normal constraints on mast cell activation, proliferation, and survival may be central to disease etiology, understanding these issues warrants attention. This review summarizes the knowledge of mast cell homeostasis controlled by IgE and the regulatory cytokines IL-4, IL-10, and TGF-beta1. Because each of these proteins plays an important role in immune responses tied to mast cell-associated disease, this group represents a potential set of factors altered in atopic or autoimmune patients. It is interesting to note, for example, that polymorphisms within each of these factors or their receptors are linked to allergic disease. By first understanding how cytokines and IgE regulate mast cell function and survival, we may then predict how these factors may function in disease onset and progression.
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PMID:Mast cell homeostasis: a fundamental aspect of allergic disease. 1743 94

The environmental contamination by dispersion of depleted uranium (DU) might result in its chronic ingestion of DU by local populations. The aim of this study was to determine if chronic ingestion of DU at low doses induces inflammatory reactions in intestine, first biological system exposed to uranium after ingestion. Experiments were performed with rats receiving uranium in drinking water (40 mg/l) during 3, 6, or 9 months. Several parameters referring to prostaglandin, histamine, cytokine, and nitric oxide (NO) pathways were assessed in ileum. Concerning the prostaglandin pathway, a twofold increase in gene expression of cyclooxygenase of type 2 was noted after 6 months, with no changes in prostaglandins levels. At the same time, a decrease in mast cell number was observed without any changes in histamine levels. Experiments on cytokines showed increased gene expression of interleukin (IL)-1beta and IL-10 at 6 months, and decreased messenger RNA level of CCL-2. This change was associated with decreased macrophage density. An opposite effect of DU was induced on neutrophils, since increased number was observed at 3 (x1.7) and 9 months (x3). The results obtained on NO pathway seemed to indicate that DU exposure inhibited this pathway (decreased endothelial NO synthase messenger RNA, inductive NO synthase activity and NO(2)(-)/NO(3)(-) levels) at 6 months. In conclusion, this study demonstrated that chronic ingestion of DU-induced time-dependent modifications of inflammatory pathways, notably in terms of immune cell content. The ultimate effects of DU contamination might be pathogenic by suppressing defense mechanisms or inducing hypersensitivity. Further experiments should be thus performed to determine real consequences on intestinal response to oral antigens.
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PMID:Modifications of inflammatory pathways in rat intestine following chronic ingestion of depleted uranium. 1756 59


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