Immunomodulation of skin cytokine secretion by house dust mite extracts.
ABSTRACT Skin contact with house dust mites may contribute to atopic dermatitis and other skin diseases. We sought to determine if molecules from house dust mites could influence the release of proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts grown in a human skin equivalent (HSE) model.
HSEs consisting of an epidermis of keratinocytes with stratum corneum over a dermis of fibroblasts in a collagen matrix were challenged with Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei mite extracts.
HSEs secreted interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, cutaneous T cell-attracting chemokine, transforming growth factor-α, granulocyte/macrophage and macrophage colony-stimulating factors and vascular endothelial cell growth factor in response to at least 1 mite extract. Extracts of different mite species stimulated HSEs to release different cytokines. Therefore, extracts of different species contained different molecules or different concentrations of similar molecules. The cytokine release profiles of cells in the HSEs were not the same as for monocultured keratinocytes and fibroblasts.
Molecules from house dust mites are capable of inducing the release of multiple proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts. Avoiding skin contact with house dust mites would reduce the possibility of mite-induced inflammation in the skin. Therefore, measures to reduce contact with mite molecules such as frequent vacuuming of upholstered furniture and carpets and laundering of clothing and bedding to remove mite molecules and allergens could reduce skin contact with mite molecules and diminish exacerbations of skin inflammation in patients with atopic dermatitis and other skin diseases.
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ABSTRACT: There have been only a few studies of how allergens cross the airway epithelium to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain several proteolytic enzymes. Group 1 allergens are cysteine peptidases, whilst those of groups 3, 6 and 9 have catalytic sites indicative of enzymes that mechanistically behave as serine peptidases. We have previously shown that the group 1 allergen Der p 1 leads to cleavage of tight junctions (TJs), allowing allergen delivery to antigen presenting cells. In this study we determined whether HDMFP serine peptidases similarly compromise the airway epithelium by attacking TJs, desmosomes and adherens junctions. Experiments were performed in monolayers of MDCK, Calu-3 or 16HBE14o-epithelial cells. Cell junction morphology was examined by 2-photon molecular excitation microscopy and digital image analysis. Barrier function was measured as mannitol permeability. Cleavage of cell adhesion proteins was studied by immunoblotting and mass spectrometry. HDMFP serine peptidases led to a progressive cleavage of TJs and increased epithelial permeability. Desmosomal puncta became more concentrated. Cleavage of TJs involved proteolysis of the TJ proteins, occludin and ZO-1. This was associated with activation of intracellular proteolysis of ZO-1. In contrast to occludin, E-cadherin of adherens junctions was cleaved less extensively. Although Calu-3 and 16HBE14o-cells expressed tethered ligand receptors for serine peptidases, these were not responsible for transducing the changes in TJs. HDMFP serine peptidases cause cleavage of TJs. This study identifies a second general class of HDM peptidase capable of increasing epithelial permeability and thereby creating conditions that would favour transepithelial delivery of allergens.Clinical & Experimental Allergy 03/2001; 31(2):279-94. · 4.79 Impact Factor
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ABSTRACT: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.Allergy 01/2005; 59(12):1318-25. · 5.88 Impact Factor
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ABSTRACT: In contrast to naive lymphocytes, memory/effector lymphocytes can access nonlymphoid effector sites and display restricted, often tissue-selective, migration behavior. The cutaneous lymphocyte-associated antigen (CLA) defines a subset of circulating memory T cells that selectively localize in cutaneous sites mediated in part by the interaction of CLA with its vascular ligand E-selectin. Here, we report the identification and characterization of a CC chemokine, cutaneous T cell-attracting chemokine (CTACK). Both human and mouse CTACK are detected only in skin by Southern and Northern blot analyses. Specifically, CTACK message is found in the mouse epidermis and in human keratinocytes, and anti-CTACK mAbs predominantly stain the epithelium. Finally, CTACK selectively attracts CLA(+) memory T cells. Taken together, these results suggest an important role for CTACK in recruitment of CLA(+) T cells to cutaneous sites. CTACK is predominantly expressed in the skin and selectively attracts a tissue-specific subpopulation of memory lymphocytes.Proceedings of the National Academy of Sciences 01/2000; 96(25):14470-5. · 9.74 Impact Factor