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Th2-type cytokine-induced mucus metaplasia decreases susceptibility of human bronchial epithelium to rhinovirus infection.

American journal of respiratory cell and molecular biology (2014-03-05)
Bogdan Jakiela, Anna Gielicz, Hanna Plutecka, Magdalena Hubalewska-Mazgaj, Lucyna Mastalerz, Grazyna Bochenek, Jerzy Soja, Rafal Januszek, Alar Aab, Jacek Musial, Mübeccel Akdis, Cezmi A Akdis, Marek Sanak
ABSTRACT

Human rhinoviruses (RVs) are a major cause of exacerbations in asthma and other chronic airway diseases. A characteristic feature of asthmatic epithelium is goblet cell metaplasia and mucus hypersecretion. Bronchial epithelium is also an important source of lipid mediators, including pro- and antiinflammatory eicosanoids. By using air-liquid interface cultures of airway epithelium from patients with asthma and nonasthmatic control subjects, we compared RV16 replication-induced changes in mRNA expression of asthma candidate genes and eicosanoid production in the epithelium with or without IL-13-induced mucus metaplasia. Mucus metaplastic epithelium was characterized by a 20-fold less effective replication of RV16 and blunted changes in gene expression; this effect was seen to the same extent in patients with asthma and control subjects. We identified ciliary cells as the main target for RV16 by immunofluorescence imaging and demonstrated that the numbers of ciliary cells decreased in RV16-infected epithelium. RV16 infection of mucociliary epithelium resulted in overexpression of genes associated with bronchial remodeling (e.g., MUC5AC, FGF2, and HBEGF), induction of cyclooxygenase-2, and increased secretion of prostaglandins. These responses were similar in both studied groups. These data indicate that structural changes associated with mucus metaplasia renders airway epithelium less susceptible to RV infection. Thus, exacerbations of the lung disease caused by RV may result from severe impairment in mucociliary clearance or activation of immune defense rather than from preferential infection of mucus metaplastic epithelium. Repeated rhinoviral infections of compromised epithelium may contribute to the remodeling of the airways.

MATERIALS
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Brand
Product Description

Supelco
Tretinoin, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Tretinoin, United States Pharmacopeia (USP) Reference Standard
Tretinoin, European Pharmacopoeia (EP) Reference Standard