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)

The increasing amounts of evidence prove that sex hormones modulate different cells function, including mast cells and lymphocytes. Dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) are both the secretory products of adrenal glands and the most abundant hormones in the systemic circulation of humans, converted then into androgens and estrogens in the periphery. DHEA may affect production of Th1 and Th2- associated cytokines, suggesting their significance in diseases where imbalanced lymphocyte activity plays the essential role, also in atopic diseases. Reduced circulating concentration of these androgens has been demonstrated in patients with immune-inflammatory diseases, including atopic eczema/dermatitis syndrome and asthma. It is unknown however, whether such changes contribute in any way to etiopathogenesis of the disorders, or are merely their consequences. Chronic urticaria, not included in the atopic triad, is a mast cell-dependent disease characterised by activation of autoimmune and inflammatory processes responding to different factors. Alterations in the immune-neuro-endocrine milieu may contribute to the development of the disease. It has been demonstrated that DHEA-S concentration is significantly lower in the peripheral circulation of patients suffering from chronic urticaria, as compared with healthy subjects. On one hand, this reflects some changes in hormonal homeostasis in the course of urticarial processes, yet on the other, suggests some possible role for this hormone in pathophysiology of the disease. In this brief review we present the available data on DHEA-S involvement in events associated with atopic allergy as well as chronic urticaria.
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PMID:Dehydroepiandrosterone and dehydroepiandrosterone sulphate in atopic allergy and chronic urticaria. 1828 94

The present review aims to elucidate the emerging role played by cannabinomimetic compounds in the control of mast cell activation. Mast cells are immune competent cells strategically localised at the sites directly interfacing with the external environment, which, in case of injury, regulate the immune response by the release of a plethora of both pre-formed and newly-synthesised mediators. However, although the main goal of mast cell activation is to initiate the inflammatory reaction, and thus maintain internal homeostasis, the consequences of dysregulated mast cell activation could be to chronically activate the inflammatory response as occurs in arthritis, inflammatory bowel diseases, atherosclerosis and asthma. Therefore, much effort has been made to develop compounds that act to prevent mast cell degranulation. Cannabinomimetic compounds (i.e. agents able to modulate endocannabinoid function) are considered as an emerging class of regulators of mast cell behaviour. We focus on the evidence for a cannabinomimetic control of both acute and chronic inflammatory disease, recognising a common mast cell origin for problems such as dermatitis, inflammatory gastrointestinal syndrome and granuloma formation. Special emphasis is provided for the recent promising results obtained with palmitoylethanolamide in human studies. In the light of evidence suggesting that the control of mast cell activation at an early time during an inflammatory process may account for its resolution, it is reasonable to propose that cannabinomimetic compounds, including palmitoylethanolamide and its congeners, could represent possible candidates for treating several chronic inflammatory diseases.
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PMID:Cannabinomimetic control of mast cell mediator release: new perspective in chronic inflammation. 1842 95

Chronic urticaria is characterized by mast cells/basophils activation which initiate the inflammatory response. Pathogenetically, the disease may in many cases represent an autoimmune phenomenon. Altered function of the neuro-endocrine-immune system due to stress and other factors has also been implicated its pathogenesis. Sex hormones modulate immune and inflammatory cell functions, including mast cell secretion, and are regarded as responsible for gender and menstrual cycle phase-associated differential susceptibility and severity of some autoimmune and inflammatory diseases. Chronic urticaria is approximately twice more frequent in women than in men. In addition, urticaria may be associated with some diseases and conditions characterized by hormonal changes, including endocrinopathy, menstrual cycle, pregnancy, menopause and hormonal contraceptives or hormone replacement therapy. Hypersensitivity reactions to endogenous or exogenous female sex hormones have been implicated in the pathogenesis of urticarial lesions associated with estrogen and autoimmune progesterone dermatitis. We observed lower serum dehydroepiandrosterone sulfate (DHEA-S) concentration in patients with chronic urticaria with positive and negative response to autologous serum skin test. Thus, the influence of fluctuations in the hormonal milieu and altered sex hormone expression on the triggering-off, maintenance or aggravation of urticaria should be taken into account. In addition, the possible impact of estrogen mimetics, in the environment and in food, on the development of disease associated with mast cell activation must be considered. This review endeavours to outline what is known about the possible influence of sex hormones in the expression of urticaria.
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PMID:Sex hormones and urticaria. 1848 75

Suitability of blood basophils for in vitro diagnosis of flea allergy dermatitis (FAD) or flea bite hypersensitivity was studied in cats. A functional in vitro test (FIT) for sensitized type I allergic effector cells was used to evaluate the degree and kinetics of in vivo basophil sensitization against flea antigens in cats under long-term flea exposure. FIT results were compared with intradermal (IDT) and serological testing. Before, during, and after weekly repeated exposure to Ctenocephalides felis; 14 cats were repetitively FIT-assessed for general and flea-specific sensitization. In three cats, flea-specific sensitization was seen before and throughout flea exposure. Five cats, although generally sensitized, never developed a flea-specific sensitization. Six cats initially FIT-negative became sensitized for flea antigen during flea infestation. Induction, upregulation, and binding of C. felis-specific sensitizing antibodies to basophils during flea challenge may explain the developing sensitization in these cats. Strong discrepancies between the levels of flea-specific circulating IgE and basophil sensitization contrasted comparable results for basophil and mast cell sensitization using FIT and IDT, respectively. Hence, the FIT might provide an immunological supplement to the clinical diagnosis of FAD in cats by elucidating the state of basophil-sensitization to flea antigens. And it may be a comfortable alternative to IDT.
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PMID:Monitoring of basophil sensitization to antigens of the cat flea (Ctenocephalides felis felis): a new tool for the diagnosis of feline flea bite hypersensitivity? 1859 63

Mast cells are known to be important effector cells in innate immune responses to bacterial infections. However, up to now, neither the mechanisms nor the relevance of mast cell degranulation in innate skin immune responses to bacteria have been adequately addressed. In this article, we show that the bacterial toxins streptolysin O (SLO) and alpha-toxin potently induce degranulation of mast cells in vitro and in vivo. Furthermore, intradermal injection of the toxins results in pronounced skin inflammation, which either resolves quickly within a few h (SLO-induced inflammation) or presents a chronic process with ongoing inflammation for weeks (alpha-toxin). Interestingly, mast cells mediated the inflammatory effects of SLO, but in contrast limited inflammatory skin responses to alpha-toxin. These findings further support the hypothesis that mast cells are critically involved in initiating and modulating optimal host responses to bacteria by either inflammatory or anti-inflammatory effects, depending on the course of the host reaction induced by the pathogen.
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PMID:Mast cells determine the magnitude of bacterial toxin-induced skin inflammation. 1864 47

The ability of Staphylococcus aureus to invade and survive within host cells is believed to contribute to its propensity to cause persistent and metastatic infections. In addition, S. aureus infections often are associated with atopic diseases such as dermatitis, rhinitis, and asthma. Mast cells, the key cells of allergic diseases, have a pivotal role in innate immunity and have the capacity of phagocytosis, and they can destroy some pathogenic bacteria. However, little is known about the ability of some other bacteria to survive and overcome mast cell phagocytosis. Therefore, we were interested in evaluating the interplay between mast cells and S. aureus. In this study, we show that human cord blood-derived mast cells (CBMC) can be infected by pathogenic S. aureus. S. aureus displayed a high adherence to mast cells as well as invasive and survival abilities within them. However, when infections were performed in the presence of cytochalasin D or when CBMC were preincubated with anti-Toll-like receptor 2 (TLR2) or anti-CD48 antibodies, the invasiveness and the inflammatory response were abrogated, respectively. Furthermore, we observed an increase of TLR2 and CD48 molecules on CBMC after S. aureus infection. The infection of CBMC with S. aureus also caused the release of tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8). Both live and killed S. aureus organisms were found to trigger TNF-alpha and IL-8 release by CBMC in a time-dependent manner. Cumulatively, these findings suggest that S. aureus internalizes and survives in mast cells. This may play an important role in infections and in atopic diseases associated with S. aureus.
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PMID:Human mast cell activation by Staphylococcus aureus: interleukin-8 and tumor necrosis factor alpha release and the role of Toll-like receptor 2 and CD48 molecules. 1864 75

Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly begins in childhood. K6PC-9p (N-(Ethyl dihydrogenphosphate)-2-hexyl-3-oxo-decanamide) is a synthetic ceramide derivative of PC-9S (N-Ethanol-2-mirystyl-3-oxo-staramide), which was known to be effective in atopic patients. In this study, we examined the effect of topical application of K6PC-9p on skin inflammation and AD-like skin lesions in mouse models. K6PC-9p dose-dependently inhibited phorbol ester-induced increase in ear thickness in BALB/c mice. Moreover, topical application of K6PC-9p suppressed dust mite extract-induced AD-like skin lesions in NC/Nga mice. Histopathological analysis revealed that both ear swelling and leucocyte infiltration were suppressed by K6PC-9p treatment. K6PC-9p also suppressed IL-4 and TNF-alpha expression in the ears and mast cell infiltration into the ears in NC/Nga mice. Further study demonstrated that K6PC-9p inhibited ConA-induced IL-4 secretion and LPS-induced macrophage activation. Taken together, our results showed that topical application of K6PC-9p exerts beneficial effects in animal model of skin inflammation and AD, suggesting that K6PC-9p might be a promising topical agent for the treatment of inflammatory skin diseases.
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PMID:Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC/Nga mice. 1872 Nov 97

Cumulative evidence suggests that the induction of the antioxidant/anti-inflammatory heme oxygenase (HO)-1 may play a protective role in allergic inflammation. HO-1 suppresses mast cell degranulation and cytokine synthesis. The up-regulation of the HO-1 pathway has a significant protective effect against airway inflammation, mucus hyper-secretion, and hyper-responsiveness in a model of allergic asthma. Moreover, HO-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells. The precise underlying mechanisms for HO-1-based protection against allergic inflammation are not yet completely understood, but appear to involve the protective effects of HO-1 by-products, such as carbon monoxide (CO), biliverdin/bilirubin and free iron. Among the HO-1 by-products, CO has been shown to mimic some protective actions of HO-1 in allergic inflammations. This article reviews the latest knowledge, recent patent and studies on the protective roles and mechanisms of HO-1/CO in inflammation and allergy.
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PMID:Heme oxygenase-1 and carbon monoxide: emerging therapeutic targets in inflammation and allergy. 1907 5

Neutralization of stratum corneum (SC) adversely impacts key epidermal functions, including permeability barrier homeostasis and SC integrity. Conversely, acidification of SC improves these functions in developmentally impaired (neonatal or aged) skin, and enhances function in normal skin. Hence, we hypothesized that acidification could alter the course of inflammatory dermatoses, which invariably exhibit an increased SC pH. Maintenance of a low pH by topical applications of the polyhydroxyl acid, lactobionic acid, during the repeated-challenge phase inhibited the development of oxazolone-induced atopic dermatitis (AD). Neither gross/histological dermatitis nor altered barrier function developed, and emergence of epidermal hyperplasia was prevented; however, cytokine generation decreased. Acidification also largely normalized the development of hapten-induced changes in eosinophil/mast cell densities, density of chemoattractant receptor-homologous molecule expressed on TH2-positive lymphocytes, and serum IgE levels. The pH-induced improvement in barrier function most likely accounts for the anti-inflammatory activity, which could be further attributed to normalization of both lamellar body secretion and lamellar bilayer formation. Acidification of SC alone substantially prevents development of barrier abnormalities and downstream immune abnormalities during the elicitation phase of murine AD. These results provide direct evidence for the "outside-inside" pathogenesis of AD and further suggest that maintenance of an acidic SC pH could prevent the emergence of AD in humans.
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PMID:Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis. 1917 39

Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor kappaB-mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor alpha, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5(-/-) embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)-like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy.
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PMID:Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. 1941 52


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