House dust mite allergens, store-operated Ca(2+) channels and asthma

屋尘螨过敏原、储存激活的Ca(2+)通道与哮喘

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Abstract

The house dust mite is the principal source of aero-allergen worldwide. Exposure to mite-derived allergens is associated with the development of asthma in susceptible individuals, and the majority of asthmatics are allergic to the mite. Mite-derived allergens are functionally diverse and activate multiple cell types within the lung that result in chronic inflammation. Allergens activate store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels, which are widely expressed in multiple cell types within the lung that are associated with the pathogenesis of asthma. Opening of CRAC channels stimulates Ca(2+)-dependent transcription factors, including nuclear factor of activated T cells and nuclear factor-κB, which drive expression of a plethora of pro-inflammatory cytokines and chemokines that help to sustain chronic inflammation. Here, I describe drivers of asthma, properties of mite-derived allergens, how the allergens are recognized by cells, the signalling pathways used by the receptors and how these are transduced into functional effects, with a focus on CRAC channels. In vivo experiments that demonstrate the effectiveness of targeting CRAC channels as a potential new therapy for treating mite-induced asthma are also discussed, in tandem with other possible approaches.

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