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Primary Nasal Epithelium Exposed to House Dust Mite Extract Shows Activated Expression in Allergic Individuals

¹ Department of Otorhinolaryngology, Academic Medical Center, Amsterdam; and ² Integrative Bioinformatics Unit, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands

Correspondence and requests for reprints should be addressed to Aram B. Vroling, MSc., Room L3-106, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands. E-mail a.b.vroling{at}amc.uva.nl

Nasal epithelial cells form the outermost protective layer against environmental factors. However, this defense is not just physical; it has been shown that epithelial cells respond by the production of inflammatory mediators that may affect local immune responses. In this research we set out to characterize potential differences between the responses of nasal epithelium from healthy and allergic individuals to house dust mite (HDM) allergen. These differences will help us to define local mechanisms that could contribute to allergic disease expression. Epithelial cells were cultured from nasal biopsies taken from five healthy and five allergic individuals. These cultures were exposed for 24 hours to culture medium containing HDM allergen, or to culture medium alone. Isolated RNA was used for microarray analysis. Gene-ontology of the response in healthy epithelium revealed mainly up-regulation of chemokines, growth factors, and structural proteins. Moreover, we saw increased expression of two transcription factors (NF-B and AP-1) and their regulatory members. The expression pattern of epithelium from allergic individuals in the absence of the HDM stimulus suggests that it is already in an activated state. Most striking is that, while the already activated NF-B regulatory pathway remained unchanged in allergic epithelium, the AP-1 pathway is down-regulated upon exposure to HDM allergen; this is contrary to what we see in healthy epithelium. Clear differences in the expression pattern exist between epithelial cells isolated from healthy and allergic individuals at baseline and between their responses to allergen exposure; these differences may contribute to the inflammatory response.

Key Words: allergy • epithelial response • innate immunity • local tissue response

CLINICAL RELEVANCE Response of epithelial cells to allergen has not before been studied on a genome expression level. Characterization of the responses will give new insight to the pathophysiology, and open roads to new treatments.