Increased expression of the aryl hydrocarbon receptor in allergic nasal mucosa, contributing to chemokine secretion in nasal epithelium

Abstract

Background: Pollutants produced by industrial and traffic-related activities have been linked to allergic responses. These noxious agents induce their effects through the aryl hydrocarbon receptor (AhR). Objective: We analyzed the expression and distribution pattern of AhR in normal and allergic nasal mucosa, and cytokine-driven regulation of its expression. The production levels of chemokine in cultured nasal epithelial cells were evaluated after stimulation with AhR ligand. Methods: The expression levels and distribution pattern of AhR in normal, mild, and moderate-severe persistent allergic nasal mucosa were assessed by using real-time polymerase chain reaction, Western blot, and immunohistochemistry. The expression levels of AhR were determined in cultured nasal epithelial cells treated with T-helper 2 cytokines. In cultured epithelial cells stimulated with 2-(10H-indole-30-carbonyl)-thiazole-4-carboxylic acid methyl ester, the expression levels of granulocyte macrophage colony-stimulating factor, thymus and activation regulated chemokine, macrophage inflammatory protein 1 alpha, monocyte chemotactic protein 1, regulated on activation normal T-cell expressed and secreted, eotaxin, and interleukin 8 were measured with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Expression of AhR was observed in normal and allergic nasal mucosa where it is distributed in the epithelial layer, submucosal glands, endothelial cells, and inflammatory cells. Its expression levels are increased in allergic nasal mucosa and upregulated after stimulation with T-helper 2 cytokines. The stimulation with 2-(10H-indole-30-carbonyl)-thiazole-4-carboxylic acid methyl ester resulted in increased production of chemokines in cultured epithelial cells. Conclusion: Analysis of the study results indicated that increased expression levels of AhR may play a role in the pathogenesis of allergic rhinitis, which contributes to chemokine production in nasal mucosa.