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Published ahead of print on September 27, 2007, doi:10.1165/rcmb.2007-0278OC

Am. J. Respir. Cell Mol. Biol., Volume 38, Number 3, March 2008, 293-299

A more recent version of this article appeared on March 1, 2008
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Submitted on July 23, 2007
Revised on September 25, 2007

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

Aram B Vroling1*, Martijs J Jonker2, Silvia Luiten1, Timo M Breit2, Wytske J Fokkens1, and Cornelis M van Drunen1

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

* To whom correspondence should be addressed. 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 allergen (HDM). 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 h to culture medium containing house dust mite 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-{kappa}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 already is in an activated state. Most striking is that, while the already activated NF-{kappa}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.







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