Mast cells in atopic dermatitis

Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Current opinion in immunology (Impact Factor: 7.48). 10/2009; 21(6):666-78. DOI: 10.1016/j.coi.2009.09.006
Source: PubMed

ABSTRACT Mast cells play as the major effector cells in immediate hypersensitivity through activation via the high-affinity IgE receptor, Fc epsilon RI, although many other functions have recently been discovered for this cell type. Given the broad array of proinflammatory mediators secreted from Fc epsilon RI-activated mast cells, as well as sensitization to allergens, IgE elevation, and increased mast cells in a majority of atopic dermatitis patients, mast cells are believed to be involved in the pathogenesis of atopic dermatitis. Numerous animal models have been used to study this epidemic disease. Here we review the recent progress to synthesize our current understanding of this disease and potential mechanisms for a mast cell's role in the disease.

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Available from: Toshiaki Kawakami, Dec 19, 2013
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    • "Mast cell activation leads to different cellular processes beyond degranulation. Different cytokines and chemokines are produced by mast cells depending on the activation signal (Kawakami et al., 2009). TNF-␣ is a well-known cytokine that mast cells can release from preformed storage or produce de novo after infection with different pathogens (St John and Abraham, 2013). "
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    ABSTRACT: Mast cells are crucial elements of the innate immune response. They reside in tissues that are commonly exposed to the external environment, such as the skin and mucosae, where they can rapidly detect the presence of pathogens and mount a potent inflammatory response that recruits other cellular effectors of the immune response. The contribution of mast cells to the immune response to viruses, bacteria, protozoa and multicellular parasites is well established, but there is scarce information about the role of these cells in fungal infections. In this study, we analyzed if mast cells are activated by Candida albicans and if the C-type lectin receptor Dectin-1 is involved in its recognition. We found that both yeasts and hyphae of C. albicans-induced mast cell degranulation and production of TNF-α, IL-6, IL-10, CCL3 and CCL4, while only yeasts were able to induce IL-1β. Mast cells also produced ROS after stimulation with both dimorphic phases of C. albicans. When mast cells were activated with yeasts and hyphae, they showed decreased expression of IκBα and increased presence of phosphorylated Syk. Blockade of the receptor Dectin-1, but not Toll-like receptor 2, decreased TNF-α production by mast cell in response to C. albicans. These results indicate that mast cells are capable of sensing the two phases of C. albicans, and suggest that mast cells participate as an early inductor of inflammation during the early innate immune response to this fungus. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Immunobiology 05/2015; 220(9). DOI:10.1016/j.imbio.2015.05.005 · 3.04 Impact Factor
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    • "For personal use only. increase in the mast cell number (Kawakami et al., 2009). Therapeutic agents for AD can affect mast cells number. "
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    ABSTRACT: Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220–350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (∼13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.
    Drug Delivery 09/2014; DOI:10.3109/10717544.2014.960981 · 2.56 Impact Factor
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    • "Although not completely understood, the aetiology of the disease is multifactorial and depends on complex interactions between genetic and environmental factors. An immune dysregulation that causes Th2-predominant inflammation and an intrinsic defect in skin barrier function are currently the two major hypotheses, both for human and canine AD [1-3]. Strong debate is still ongoing on whether changes observed in skin barrier function are the cause or consequence of AD inflammatory changes [4]. "
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    ABSTRACT: Despite the precise pathogenesis of atopic dermatitis (AD) is still unknown, an immune dysregulation that causes Th2-predominant inflammation and an intrinsic defect in skin barrier function are currently the two major hypotheses, according to the so-called outside-inside-outside model. Mast cells (MCs) are involved in AD both by releasing Th2 polarizing cytokines and generating pruritus symptoms through release of histamine and tryptase. A link between MCs and skin barrier defects was recently uncovered, with histamine being found to profoundly contribute to the skin barrier defects.Palmitoylethanolamide and related lipid mediators are endogenous bioactive compounds, considered to play a protective homeostatic role in many tissues: evidence collected so far shows that the anti-inflammatory effect of palmitoylethanolamide depends on the down-modulation of MC degranulation.Based on this background, the purpose of the present study was twofold: (a) to determine if the endogenous levels of palmitoylethanolamide and other bioactive lipid mediators are changed in the skin of AD dogs compared to healthy animals; (b) to examine if MC number is increased in the skin of AD dogs and, if so, whether it depends on MC in-situ proliferation. The amount of lipid extract expressed as percent of biopsy tissue weight was significantly reduced in AD skin while the levels of all analyzed bioactive lipid mediators were significantly elevated, with palmitoylethanolamide showing the highest increase.In dogs with AD, the number of MCs was significantly increased in both the subepidermal and the perifollicular compartments and their granule content was significantly decreased in the latter. Also, in situ proliferation of MCs was documented. The levels of palmitoylethanolamide and other bioactive lipid mediators were shown to increase in AD skin compared to healthy samples, leading to the hypothesis that they may be part of the body's innate mechanisms to maintain cellular homeostasis when faced with AD-related inflammation. In particular, the increase may be considered a temptative response to down-regulating the observed elevation in the number, functionality and proliferative state of MCs in the skin of AD dogs. Further studies are warranted to confirm the hypothesis.
    BMC Veterinary Research 01/2014; 10(1):21. DOI:10.1186/1746-6148-10-21 · 1.78 Impact Factor
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