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)

Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL-10, and IL-13. When exogenous rIL-12 was administered to T. spiralis-infected NIH mice, this resulted in significant suppression of intestinal mast cell responses, delayed worm expulsion, increased muscle larvae burdens, and a transient, but significant decrease in early Th2 cytokine secretion. rIL-12 treatment also altered chemokine expression in the jejunal mucosa. The effects of exogenous IL-12 administration were largely independent of IFN-gamma as shown by rIL-12 treatment of IFN-gamma knockout mice. Hence, IL-12 may play a significant biological role as a direct negative regulator of intestinal Th2 responses and may act to promote the survival of intestinal parasites in vivo also in the absence of IFN-gamma.
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PMID:IFN-gamma-independent effects of IL-12 during intestinal nematode infection. 1450 Jun 67

IFN-gamma rapidly primes the macrophage via JAK1/2-STAT1 pathway so that it can subsequently undergo a slower classical type 1 activation upon exposure to T helper (Th)1 cytokines such as IFNgamma or other activators, including tumor necrosis factor and lipopolysaccharide, e.g. in intracellular killing of phagocytosed Mycobacterium tuberculosis. If instead it is driven by Th2 cytokines interleukin (IL)-4 and IL-13, it undergoes alternate type 2 activation, which enhances endocytotic antigen uptake and presentation, mast cell and eosinophil involvement and type 2 granuloma formation, e.g. in response to parasitic and extracellular pathogens. Particle-induced macrophage activation was shown to differ from classical and alternate activation, showing in DNA microarray experiments (complete linkage/ Euclidean distance metric analysis) upregulation of nonsecreted structural/signaling molecules and lack of secreted proinflammatory cyto- and chemokines. The switch-off (deactivation) of already activated macrophages is an active, controlled process in which IL-10 and corticosteroids play important roles and to which 15dPGJ2, PGA1/2 and vasoactive intestinal peptide often contribute.
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PMID:Regulation of macrophage activation. 1462 80

Mast cells are recognized not only as the major effector cells of type I hypersensitivity reactions but also as an important player of innate immune response against bacterial infection. Type I IFNs are also involved in the response against bacterial infection. However, the role of type I IFNs and their associated Janus kinase Tyk2 in mast cell functions remains to be determined. In this study, we addressed this issue using Tyk2-deficient (Tyk2(-/-)) bone marrow-derived mast cells (BMMCs). When BMMCs from wild-type (WT) mice were stimulated with IFN-alpha, they expressed mRNA for IFN-gamma-inducible protein 10 (IP-10) and monocyte chemoattractant protein-5 (MCP-5). Interestingly, IFN-alpha-induced expression of IP-10 and MCP-5 was severely decreased in Tyk2(-/-) BMMCs. In addition, IFN-alpha-induced Stat1 phosphorylation was decreased in Tyk2(-/-) BMMCs. On the other hand, IFN-alpha-induced Stat1 phosphorylation and IP-10 and MCP-5 expression were normal in Tyk2(-/-) fibroblasts. These results indicate that IFN-alpha induces the expression of TNF-alpha and the chemokines IP-10 and MCP-5 in mast cells and thatTyk2 plays a nonredundant role in IFN-alpha signaling in mast cells.
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PMID:Tyk2 is essential for IFN-alpha-induced gene expression in mast cells. 1516 80

Infection of a susceptible host with Leishmania, a protozoan parasite, causes the disease leishmaniasis, which is characterized by neutrophil, eosinophil, macrophage, lymphocyte and mast cell infiltration into the infected tissue followed by parasite growth. Although the roles played by other cells in leishmaniasis are known, the role of mast cells remains to be ascertained. Here, we demonstrate that Leishmania regulates mast cell infiltration to the site of infection, mast cell production and mast cell function resulting in differential growth of the parasite in resistant (C57BL/6 or CBA/T6T6) and susceptible (BALB/c) macrophages. An interleukin-3-dependent augmentation in mast cell committed progenitors is observed in BALB/c but not in C57BL/6 mice during Leishmania infection. The mast cell supernatants inhibit IFN-gamma-dependent restriction of Leishmania growth in macrophages in BALB/c mice whereas the reverse phenomenon occurs in C57BL/6 mice. Our data reveals a different facet of host-pathogen interaction.
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PMID:Mast cells at the host-pathogen interface: host-protection versus immune evasion in leishmaniasis. 1519 39

T-helper 1 (TH1) (interferon-gamma [IFN-gamma]) and TH2 (interleukin-4 [IL-4] and IL-5) cytokines have been variably reported to alter human mast cell numbers in complex culture systems. The effects of these cytokines on the kinetics of cell division and cell death are unknown, and their effect on mast cell behavior is relevant to anticipate the consequences of in vivo strategies that alter cytokine levels. To determine the effect of these cytokines on stem cell factor (SCF)-dependent human mast cell production, we used high-resolution tracking of cell division and correlated the results with cell apoptosis, expression of Kit, and mast cell degranulation. When IFN-gamma, IL-5, or IL-4 was administered over 8 weeks, we found each cytokine decreased the mast number through a different mechanism. IFN-gamma inhibited early progenitor cell division, IL-4 down-regulated early Kit expression, and IL-5 blocked later cell division. Further, IL-4 and IFN-gamma had the greatest suppressive effect on degranulation and FcepsilonRI expression. When these cytokines were administered to mature mast cells, IFN-gamma and IL-5 had no effect on degranulation and cell division, but IL-4 induced division and potentiated FcepsilonRI-mediated degranulation. Thus, exposure of human mast cells to IL-4, IL-5, and IFN-gamma during growth and differentiation generally down-regulated mast cell number and function, whereas IL-4 increased mature mast cell division and degranulation.
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PMID:High-resolution tracking of cell division demonstrates differential effects of TH1 and TH2 cytokines on SCF-dependent human mast cell production in vitro: correlation with apoptosis and Kit expression. 1536 34

Chronic stress plays an important role in the development and exacerbation of symptoms in functional gastrointestinal disorders. To better understand the mechanisms underlying this relationship, we aimed to characterize changes in visceral and somatic nociception, colonic motility, anxiety-related behavior, and mucosal immune activation in rats exposed to 10 days of chronic psychological stress. Male Wistar rats were submitted daily to either 1-h water avoidance (WA) stress or sham WA for 10 consecutive days. The visceromotor response to colorectal distension, thermal somatic nociception, and behavioral responses to an open field test were measured at baseline and after chronic WA. Fecal pellets were counted after each WA stress or sham WA session as a measure of stress-induced colonic motility. Colonic samples were collected from both groups and evaluated for structural changes and neutrophil infiltration, mast cell number by immunohistochemistry, and cytokine expression by quantitative RT-PCR. Rats exposed to chronic WA (but not sham stress) developed persistent visceral hyperalgesia, whereas only transient changes in somatic nociception were observed. Chronically stressed rats also exhibited anxiety-like behaviors, enhanced fecal pellet excretion, and small but significant increases in the mast cell numbers and the expression of IL-1beta and IFN-gamma. Visceral hyperalgesia following chronic stress persisted for at least a month. Chronic psychological stress in rats results in a robust and long-lasting alteration of visceral, but not somatic nociception. Visceral hyperalgesia is associated with other behavioral manifestations of stress sensitization but was only associated with minor colonic immune activation arguing against a primary role of mucosal immune activation in the maintenance of this phenomenon.
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PMID:Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia. 1574 11

DNA microarray hybridization was used to measure the changes of mRNA levels over time during the development of delayed pigmented spots on the dorsal skin of F1 mice of HR-1 x HR/De. Upregulation of a number of interferon (IFN)-gamma-stimulated genes was detected in delayed pigmented lesions, suggesting that IFN-gamma may play a pivotal role in the development of delayed pigmented spots in this model. Upregulation of these genes was further supported by the increased protein expression level of IFN-gamma in the lesions. Epidermal infiltration of CD8(+) T lymphocytes and mast cell accumulation in the dermis were observed in delayed pigmented spots. Genes encoding chemokines such as monocyte chemoattractant protein-2 (MCP-2), IFN-inducible protein 10 (IP-10), and monokine induced by IFN-gamma (MIG) were among those upregulated by IFN-gamma. We hypothesize that chemokines produced in the epidermis induce migration of inflammatory cells, such as T lymphocytes, mast cells, and macrophages, to the vicinity of melanocytes. Keratinocytes, T lymphocytes, mast cells, and macrophages would become involved in an interactive network, providing a suitable local environment for melanocyte activation. In this environment, melanocytes are exposed to an extensive array of secreted mediators. Reciprocal activation among these cells to maintain this interactive network results in constitutive melanocyte activation and chronic melanin synthesis in delayed pigmented lesions.
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PMID:Upregulation of the IFN-gamma-stimulated genes in the development of delayed pigmented spots on the dorsal skin of F1 mice of HR-1 x HR/De. 1585 48

Mast cells are critical effectors of allergic disease, and are now implicated in immune responses observed in arthritis, multiple sclerosis, and heart disease. Because of their role in inflammation, understanding how mast cells develop is of clinical importance. In this study we determined the effects of IFN-gamma on mast cell survival. Using in vitro culture of bone marrow cells in IL-3 plus stem cell factor, we found that the addition of IFN-gamma induced apoptosis, as exhibited by the presence of subdiploid DNA and caspase activation. IFN-gamma-mediated apoptosis was Stat1-dependent, and was accompanied by loss of mitochondrial membrane potential. Apoptosis was reduced in cultures of bone marrow cells derived from p53- or Bax-deficient mice, as well as H2K-Bcl-2 transgenic mice. IFN-gamma hyperresponsiveness has been shown to result in inflammatory disease and death in mice lacking the regulatory protein suppressor of cytokine signaling (SOCS)-1. Bone marrow cells from SOCS-1 knockout (KO) mice failed to give rise to viable mast cells after culture in IL-3 plus stem cell factor, with profound apoptosis occurring as the cultures matured. However, bone marrow cells lacking both SOCS-1 and IFN-gamma survived normally. This in vitro defect in mast cell development was recapitulated in vivo. SOCS-1 KO mice demonstrated a 67% decrease in peritoneal mast cell numbers relative to wild-type mice, a deficiency that was reversed in SOCS-1/IFN-gamma KO mice. These data demonstrate the potent regulatory effects of IFN-gamma on mast cell survival and show that this cytokine can elicit mast cell death in vitro and in vivo.
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PMID:IFN-gamma induces apoptosis in developing mast cells. 1611 87

Gammi-danguieumja (GD) is clinically used in South Korea for treating atopic dermatitis. However, its effects in experimental models remain unknown. We investigated a possible effect of GD on cytokines production using human T cell line (MOLT-4) or human mast cell line. As a result, GD (0.01 mg/mL)-containing medium in stimulated culture supernatants increased IL-2 and IFN-gamma, and decreased IL-4 secretion in MOLT-4. GD (0.01-1 mg/mL)-containing medium in stimulated culture supernatants dose-dependently and significantly decreased IL-8, IL-13, and tumor necrosis factor-alpha secretion on the phorbol 12-myristate 13-acetate and A23187-stimulated HMC-1. In addition, GD inhibited histamine release from activated mast cells. These results suggest that GD contributes to the regulation of atopic allergic reactions.
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PMID:Regulatory effects of cytokine production in atopic allergic reaction by gammi-danguieumja. 1613 3

Once considered to be of sole importance in allergy and parasitic infections, the role of mast cells in other pathologic and protective immune responses is becoming increasingly evident. We previously demonstrated that mast cells contribute to the severity of EAE, the rodent model of multiple sclerosis. Here we show that one mode of mast cell action is through effects on the autoreactive T cell response. Early indices of both peripheral CD4 and CD8 T cell activation, including IFN-gamma production and increases in CD44 and CD11a expression, are attenuated in mast cell-deficient (W/Wv) mice after myelin oligodendrocyte glycoprotein(35-55) priming when compared to WT animals. Reduced infiltrates of activated T cells in the central nervous system are also observed. Importantly, selective repletion of the mast cell compartment restores most T cell responses in the lymph nodes and the central nervous system, correlating with reconstitution of severe disease. The adoptive transfer of WT-derived encephalitogenic T cells results in significantly less severe disease in W/Wv recipients, indicating that mast cells also exert potent effects after the initial T cell response is generated. Our data provide the first in vivo evidence that mast cells can significantly influence T cell responses and suggest that mast cells exacerbate disease during both the inductive and effector phases.
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PMID:Mast cells are required for optimal autoreactive T cell responses in a murine model of multiple sclerosis. 1628 14


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