Cookson WThe immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol 4:978-988

Human Genetics, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
Nature reviews. Immunology (Impact Factor: 34.99). 01/2005; 4(12):978-88. DOI: 10.1038/nri1500
Source: PubMed


Asthma and eczema (atopic dermatitis) are the most common chronic diseases of childhood. These diseases are characterized by the production of high levels of immunoglobulin E in response to common allergens. Their development depends on both genetic and environmental factors. Over the past few years, several genes and genetic loci that are associated with increased susceptibility to asthma and atopic dermatitis have been described. Many of these genes are expressed in the mucosa and epidermis, indicating that events at epithelial-cell surfaces might be driving disease processes. This review describes the mechanisms of innate epithelial immunity and the role of microbial factors in providing protection from disease development. Understanding events at the epithelial-cell surface might provide new insights for the development of new treatments for inflammatory epithelial disease.

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    • "Of the various proinflammatory mediators, nitrite and PGE2 have been found to be important in several physiological processes, including vasodilation, neurotransmission, blood coagulation, and immune regulation [19]. NO is synthesized by inducible NO synthase (iNOS), while PGE2 is produced by cyclooxygenase 2 (COX-2) [20,21]. They aggravate the inflammatory responses of atopic lesions, which are important feature is of atopic dermatitis [22]. "
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    ABSTRACT: Morus alba, a medicinal plant in Asia, has been used traditionally to treat diabetes mellitus and hypoglycemia. However, the effects of M. alba extract (MAE) on atopic dermatitis have not been verified scientifically. We investigated the effects of MAE on atopic dermatitis through in vitro and in vivo experiments. We evaluated the effects of MAE on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7, as well as thymus and activation-regulated chemokine (TARC/CCL17) in HaCaT cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for four weeks, and the protective effects of MAE were investigated by measuring the severity of the skin reaction on the back and ears, the plasma levels of immunoglobulin E (IgE) and histamine, and histopathological changes in the skin on the back and ears. MAE suppressed the production of NO and PGE2 in RAW 264.7 cells, as well as TARC in HaCaT cells, in a dose-dependent manner. MAE treatment of NC/Nga mice reduced the severity of dermatitis and the plasma levels of IgE and histamine. MAE also reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration in the skin on the back and ears. Our results suggest that MAE has potent inhibitory effects on atopic dermatitis-like lesion and may be a beneficial natural resource for the treatment of atopic dermatitis.
    BMC Complementary and Alternative Medicine 04/2014; 14(1):139. DOI:10.1186/1472-6882-14-139 · 2.02 Impact Factor
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    • "Therefore, if the severity of AD is aggravated, it will have a greater impact on human health. What’s more, both AD and asthma share an “atopy” phenotype that includes a Th2 inflammation with eosinophilia and hyper-IgE [11], [12]. Contact hypersensitivity (CHS) is a common type of AD. "
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    ABSTRACT: During the last few decades, the prevalence of allergic skin diseases, asthma and rhinitis, has increased worldwide. Introduction of environmental chemicals with aggravation effects may play a part in this increase. The artificial chemical product dibutyl phthalate (DBP) is used in many products used in daily life. Dermal exposure to DBP is a common (but easily neglected) exposure pattern. In this study, we examined the aggravation effect of long-term dermal exposure to DBP in a T-helper type 2 (Th2) model of contact hypersensitivity (CHS) in mice, and sought the potential molecular mechanisms. Experimental tests were conducted after 40-day dermal exposure to saline or three concentrations of DBP and subsequent three times of sensitization with 0.5% fluorescein isothiocyanate (FITC) or vehicle. The results of immunological and inflammatory biomarkers (total-immunoglobulin (Ig)E and Th cytokines) as well as histopathological examination and measurement of ear swelling supported the notion that high doses of DBP may promote and aggravate atopic dermatitis. Increased expression of thymic stromal lymphopoietin (TSLP) in this mouse model suggested that TSLP might be one of the molecular mechanisms of the aggravation effect induced by DBP. Together, these results indicated that long-term dermal exposure to types of environmental toxins such as phthalates may endow an atopic predisposition in animals or humans. In addition, the high expression of TSLP in the mouse model demonstrated that TSLP might have an important role in the aggravation effect. This result could help to provide effective prevention strategies against atopic diseases such as atopic dermatitis (AD).
    PLoS ONE 02/2014; 9(2):e87887. DOI:10.1371/journal.pone.0087887 · 3.23 Impact Factor
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    • "Airway epithelial cells not only provide a physical barrier to potentially harmful insults but they also play a significant role in the first line of immunological defence. There is increasing evidence that allergic diseases such as asthma are associated with epithelial disorders and, furthermore, that a primary abnormality of the airway epithelium may be central to disease causation [1], [2]. Chronic inflammation and airway remodelling are the main characteristics of asthma however they have been observed to occur in young children before asthma has become firmly established [3], [4]. "
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    ABSTRACT: Differentiated paediatric epithelial cells can be used to study the role of epithelial cells in asthma. Nasal epithelial cells are easier to obtain and may act as a surrogate for bronchial epithelium in asthma studies. We assessed the suitability of nasal epithelium from asthmatic children to be a surrogate for bronchial epithelium using air-liquid interface cultures. Paired nasal and bronchial epithelial cells from asthmatic children (n = 9) were differentiated for 28 days under unstimulated and IL-13-stimulated conditions. Morphological and physiological markers were analysed using immunocytochemistry, transepithelial-electrical-resistance, Quantitative Real-time-PCR, ELISA and multiplex cytokine/chemokine analysis. Physiologically, nasal epithelial cells from asthmatic children exhibit similar cytokine responses to stimulation with IL-13 compared with paired bronchial epithelial cells. Morphologically however, nasal epithelial cells differed significantly from bronchial epithelial cells from asthmatic patients under unstimulated and IL-13-stimulated conditions. Nasal epithelial cells exhibited lower proliferation/differentiation rates and lower percentages of goblet and ciliated cells when unstimulated, while exhibiting a diminished and varied response to IL-13. We conclude that morphologically, nasal epithelial cells would not be a suitable surrogate due to a significantly lower rate of proliferation and differentiation of goblet and ciliated cells. Physiologically, nasal epithelial cells respond similarly to exogenous stimulation with IL-13 in cytokine production and could be used as a physiological surrogate in the event that bronchial epithelial cells are not available.
    PLoS ONE 01/2014; 9(1):e85802. DOI:10.1371/journal.pone.0085802 · 3.23 Impact Factor
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