Mechanisms of Occupational Asthma : Not all Allergens are Equal(<Special Issue>Report of the 13th Annual Meeting of the Japanese Society of Immunotoxicology)
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概要
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Asthma is a heterogeneous lung disorder characterized by airway obstruction, inflammation and eosinophil infiltration into the lung. Both genetics and environmental factors influence the expression of asthma, and not all asthma is the result of a specific immune response to allergen. Numerous asthma phenotypes have been described, including occupational asthma, and therapeutic strategies for asthma control are similar regardless of phenotype. We hypothesized that mechanistic pathways leading to asthma symptoms in the effector phase of the disorder differ with the inciting allergen. Since route of allergen exposure can influence mechanistic pathways, mice were sensitized by identical routes with a high molecular weight occupational allergen ovalbumin and a low molecular weight occupational allergen trimellitic anhydride (TMA). Different statistical methods with varying selection criteria resulted in identification of similar candidate genes. Array data are intended to provide candidate genes for hypothesis generation and further experimentation. Continued studies focused on genes showing minimal changes in the TMA-induced model but with clear up-regulation in the ovalbumin model. Two of these genes, arginase 1 and eotaxin 1 are the focus of continuing investigations in mouse models of asthma regarding differences in mechanistic pathways depending on the allergen. Microarray data from the ovalbumin and TMA model of asthma were also compared to previous data using Aspergillus as allergen to identify putative asthma 'signature genes', i.e. genes up-regulated with all 3 allergens. Array studies provide candidate genes to identify common mechanistic pathways in the effector phase, as well as mechanistic pathways unique to individual allergens.
著者
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REGAL Jean
Department of Biochemistry and Molecular Biology, University of Minnesota Medical School
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GREENE Amy
Department of Biochemistry and Molecular Biology, University of Minnesota Medical School
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REGAL Ronald
Department of Mathematics and Statistics, College of Science and Engineering, University of Minnesot
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Regal Ronald
Department Of Mathematics And Statistics College Of Science And Engineering University Of Minnesota
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Regal Ronald
米国
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Regal Jean
Department Of Biochemistry And Molecular Biology University Of Minnesota Medical School
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Greene Amy
Department Of Biochemistry And Molecular Biology University Of Minnesota Medical School