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)

Atopic dermatitis, allergic rhinitis, and bronchial asthma are allergic immune disorders characterized by a predominance of T helper 2 (Th2) cells, the resulting elevation of allergen-specific immunoglobulin E (IgE), and mast cell- and eosinophil-associated inflammation. The cytokine environment at the site of the initial antigen stimulation determines the direction of helper T-cell differentiation into Th1 or Th2 cells. Therefore, negative regulators of cytokine signaling, suppressors of cytokine signaling (SOCS) proteins, play an important role in Th2-mediated allergic responses through the control of the balance between Th1 and Th2 cells. SOCS3 and SOCS5 are predominantly expressed in Th2 and Th1 cells, respectively, and they reciprocally inhibit the Th1 and Th2 differentiation processes. In this article, we discuss the role of SOCS3 and SOCS5 proteins in atopic asthma and allergic conjunctivitis and explore the potential of SOCS proteins as targets for therapeutic strategies in allergic disorders.
Curr Allergy Asthma Rep 2006 Feb
PMID:Suppressor of cytokine signaling 3 (SOCS3) in Th2 cells evokes Th2 cytokines, IgE, and eosinophilia. 1647 92

Mast cells play a central role in innate immunity and in orchestrating the asthmatic response. Current medication relies on beta-agonists to relieve bronchoconstriction and steroids to reduce inflammation. However, recently drugs such as leukotriene-receptor antagonists and anti-immunoglobulin E have come on to the market. In this paper, a number of potential targets for modifying mast cell activation in asthma are reviewed. Some are already under study, including clinical trials (eg, tryptase inhibitors); others are more speculative (eg, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity). In each case, where data are available, the action of the agents on human lung mast cells is described.
Curr Allergy Asthma Rep 2006 May
PMID:New targets for modifying mast cell activation in asthma. 1657 76

Chronic urticaria (CU) is a relatively common but vexing disease. The pathophysiology is based on the cutaneous mast cell release of mediators, predominantly histamine. Release can be induced via specific immunoglobulin E (IgE), components of complement activation and nonspecifically by various compounds including endogenous peptides, endorphins, and enkephalins. In >30% of CU patients, autoimmune phenomena have been found, characterized by positive autologous serum skin test, antibodies to the alpha-subunit of the basophil IgE receptor, to IgE itself, and, perhaps, the most clinically relevant, thyroid autoimmunity. Studies suggest that the products of the activated immune system can lower the cutaneous mast cell release threshold, possibly allowing activation by endogenous compounds. The resulting release of mediators produces the clinical picture of recurrent hives. Although the goal of management of CU is the identification of a treatable cause, in most CU patients, especially adults, a cause is not frequently found. Identified causes include drugs, foods, infections, immune complex production leading to urticarial vasculitis, autoantibody production, and underlying autoimmune disease, particularly autoimmune thyroiditis. The treatment of the thyroiditis with suppressive doses of thyroid hormone often results in the remission of the CU. Given the marginally effective and sometimes dangerous medical therapy available for CU, a systematic and thorough approach to identify a treatable cause in difficult CU patients is warranted.
Allergy Asthma Proc
PMID:Chronic urticaria: pathophysiology and etiology, or the what and why. 1672 23

Chronic urticaria is a debilitating skin disease that is believed to have an underlying autoimmune etiology in 35% to 50% of cases. Patients with autoimmune urticaria have functional antibodies in their sera that release histamine from basophils and mast cells. The C5a component of complement is required for mast cell degranulation in this process and at least augments basophil histamine release. In this article, the evidence that is key to our understanding of autoimmunity and complement in the pathogenesis of a subset of patients with chronic urticaria is outlined. Some of the issues in testing for and treating autoimmune urticaria are discussed.
Curr Allergy Asthma Rep 2006 Jul
PMID:Autoimmunity and complement in the pathogenesis of chronic urticaria. 1682 77

Recent advances in our understanding of mast cell biology and disease resulted in identification of important differences in expression of mast cell surface antigens in normal and neoplastic mast cells. Most notably, detection of aberrant expression of CD25 and CD2 on the surface of neoplastic mast cells but not on their normal counterparts leads to the inclusion of this immunophenotypic abnormality in the World Health Organization's diagnostic criteria for systemic mastocytosis. Aberrant mast cell surface marker expression can be detected in the bone marrow aspirate by flow cytometry, even in patients with limited disease that lacks histopathologically detectable aggregates of mast cells in bone marrow biopsy sections. Flow cytometric analysis of bone marrow mast cells is therefore a sensitive method of diagnosis of mast cell disease and is expected to find increasing use in determining response to emerging mast cell cytoreductive therapies.
Curr Allergy Asthma Rep 2006 Jul
PMID:Urticaria pigmentosa and mastocytosis: the role of immunophenotyping in diagnosis and determining response to treatment. 1682 80

Allergic diseases, including asthma, are chronic inflammatory disorders originating from an aberrant immune response to innocuous antigens in our environment (allergens). In susceptible individuals, sensitization to allergen leads to the induction of allergen-specific T-helper type 2 (Th2) responses and immunoglobulin E (IgE) production. Subsequent challenge with allergen results in IgE-mediated mast cell activation and the recruitment and activation of effector cells, leading to clinical symptoms of disease. In this review, we discuss evidence that the anti-inflammatory cytokine interleukin-10 (IL-10) offers therapeutic promise for the control of asthma and allergy. We highlight the potential role of IL-10 secretion by a specialized T-cell subset, T regulatory cells, to prevent allergic inflammation in healthy individuals and to provide long-term relief from disease symptoms in allergic patients.
Curr Allergy Asthma Rep 2006 Sep
PMID:Interleukin-10-secreting regulatory T cells in allergy and asthma. 1689 97

Allergic diseases are common problems affecting 20% to 30% of the US population. Mast cells and basophils are the primary effector cells mediating allergic inflammation through the triggering of membrane immunoglobulin E receptors (FceRI) with antigen. Allergen immunotherapy is used as one treatment for allergic disease and results in the inhibition of mast cell and basophil responses through unknown mechanisms. In this review, we examine potential mechanisms that could result in blunted human mast cell/basophil functional responses, strategies aimed at using these mechanisms to develop new immunologically based therapies, and recent findings that have broad implications toward our understanding of how mast cells/basophils become desensitized.
Curr Allergy Asthma Rep 2006 Sep
PMID:New approaches to allergen immunotherapy. 1689 6

Increased levels of IL-6 are documented in asthma, but its contribution to the pathology is unknown. Asthma is characterized by airway wall thickening due to increased extracellular matrix deposition, inflammation, angiogenesis, and airway smooth muscle (ASM) mass. IL-6 binds to a specific membrane-bound receptor, IL-6 receptor-alpha (mIL-6Ralpha), and subsequently to the signaling protein gp130. Alternatively, IL-6 can bind to soluble IL-6 recpetor-alpha (sIL-6Ralpha) to stimulate membrane receptor-deficient cells, a process called trans-signaling. We discovered that primary human ASM cells do not express mIL-6Ralpha and, therefore, investigated the effect of IL-6 trans-signaling on the pro-remodeling phenotype of ASM. ASM required sIL-6Ralpha to activate signal transducer and activator 3, with no differences observed between cells from asthmatic subjects compared with controls. Further analysis revealed that IL-6 alone or with sIL-6Ralpha did not induce release of matrix-stimulating factors (including connective tissue growth factor, fibronectin, or integrins) and had no effect on mast cell adhesion to ASM or ASM proliferation. However, in the presence of sIL-6Ralpha, IL-6 increased eotaxin and VEGF release and may thereby contribute to local inflammation and vessel expansion in airway walls of asthmatic subjects. As levels of sIL-6Ralpha are increased in asthma, this demonstration of IL-6 trans-signaling in ASM has relevance to the development of airway remodeling.
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PMID:Effect of IL-6 trans-signaling on the pro-remodeling phenotype of airway smooth muscle. 1693 45

Mast cells (MCs) are important effector cells in mucosal defense and allergic inflammation. Lymphoid tissues such as tonsils and adenoids also have modest numbers of MCs. However, the role of MCs in lymphoid tissues is not well known. In this study, we showed the local distribution of MCs in tonsils from IgE-mediated allergic or nonallergic donors, studied their ultrastructure, and specified their surrounding cell types. Tonsils were obtained from IgE-mediated allergic or nonallergic donors suffering from chronic tonsillitis or hyperplastic tonsils. The localization and distribution of MCs and IgE binding to MCs were determined by immunohistochemistry using antibodies against tryptase, c-kit, and IgE. In addition, mast cell structure was examined using electron microscopy. In both allergic and nonallergic donors, MCs were distributed mainly in the interfollicular area and the perivascular area of connective tissue. We found that the total number of MCs in tonsils was almost the same in both donor groups. However, the number of MCs in the interfollicular area was significantly higher in nonallergic versus allergic donors. Moreover, the electron microscopy revealed that MCs localized in perivascular areas of connective tissue have scroll-type granules, and MCs in the interfollicular areas contained both particle and scroll-type granules. In addition, the MCs that were surrounded by CD4+ lymphocytes in the interfollicular area showed empty granules, whereas MCs in the perivascular area, not surround by CD4+, were intact. This implies that these MCs were degranulated, and this probably was caused by CD4+ cells. Taken together, these findings suggest that tonsillar MCs distribute differently in allergic and nonallergic donors, and that MCs in the interfollicular area might be activated by direct contact with CD4+ T cells.
Allergy Asthma Proc
PMID:Comparison of human tonsillar mast cell localization and ultrastructural observations between IgE-mediated allergic and nonallergic donors. 1706 73

Mastocytosis is characterized by pathologic mast cell accumulation and activation in tissues. Establishment of objective histopathologic and molecular criteria for diagnosis of mastocytosis has allowed sensitive detection of mast cells with aberrant features in patients presenting with suspected mast cell activation symptoms. Frequent detection of the D816V c-kit tyrosine kinase mutation in mastocytosis has led to evaluation of small-molecular-weight tyrosine kinase inhibitors as mast cell cytoreductive agents. In vitro experiments, however, showed that mast cells carrying the D816V c-kit mutation were resistant to the prototypical tyrosine kinase inhibitor imatinib. Efficacy of newer generation tyrosine inhibitors in mast cell disease is currently being evaluated.
Curr Allergy Asthma Rep 2007 Jul
PMID:Mastocytosis: advances in diagnosis and treatment. 1754 45


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