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

Abstract

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-kappaB 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-kappaB 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.

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients

“…A large body of previous work in type I pollen allergies has focused on aberrant immunoresponses. [1][2][3][4][5][6] Although the role of epithelium as the first line of defense against allergens has recently been emphasized, [7][8][9] its true role is far from clear. We have already demonstrated the early in vivo leukocyte response after Bet v 1 pollen allergen challenge in human subjects.…”

Neuronal Differentiation Capability of Nasal Polyps of Chronic Rhinosinusitis

“…Nasal stem cells should be expected in the nasal epithelium, because it is constantly encountered to environmental factors like allergens, bacteria, or viruses, and is the initial site of injury from these factors (Vroling et al 2008;Yu et al 2012). Actually, we were able to identify different (Pezato et al 2016b).…”

“…Under normal conditions, GM-CSF is a cytokine that induces the proliferation, chemotactic migration of astrocytes, and microglia, and has a neuroprotective effect (Guillemin et al 1996;Lee et al 1994;Schäbitz et al 2008), but it was also secreted by human oligodendrocytes, which were generated from human neural stem cells . The nasal epithelium is the first barrier against environmental factors like allergens, bacteria, or viruses, and responds by producing cytokines which mediate the recruitment of immunocompetent cells (Vroling et al 2008). This leads to (chronic) inflammatory conditions and the epithelium must regenerate to restore its defensive functions (Watelet et al 2006).…”

“…The nasal epithelium is constantly encountered to environmental factors like allergens, bacteria, or viruses, and is the first line of defense against these factors, but it serves not only as physical barrier. Nasal epithelial cells are able to detect and respond to environmental signals by producing cytokines which mediate the recruitment of immunocompetent cells and create a micro-environment for these cells (Vroling et al 2008).…”

The Allergic Airway Inflammation Repository - a user-friendly, curated resource of mRNA expression levels in studies of allergic airways

“…These studies have been performed on CD4 + and CD8 + T cells, PBMC and epithelial cells from different levels of the respiratory tract (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The database also includes a study of monozygotic twins, discordant for seasonal allergic rhinitis (14).…”