Our primary objective was to investigate the possible contribution of controller medications to asthmatic airway remodeling, by (1) comparing the apoptotic and necrotic effects of several corticosteroids and montelukast on cultured airway human bronchial surface epithelial (16HBE) and submucosal (Calu3) cells; (2) measuring epithelial shedding potential and desmosome length in response to a cytokine challenge, with or without co-administered corticosteroids; and (3) studying corticosteroids and montelukast effects on inter-cellular adhesion molecule (ICAM) expression in both 16HBE and human umbilical vein endothelial cells (HUVEC). For this purpose, apoptosis, necrosis, and ICAM expression were quantified by flow cytometry, with 16HBE cells sensitive to both the apoptotic and necrotic effects of dexamethasone and montelukast; Calu3 cells sensitive only to budesonide. Transmission electron microscopy revealed decreased desmosome length in the presence of cytokines (TNF-alpha and INF-gamma), with corticosteroids counteracting this reduction. Dexamethasone, beclomethasone, and montelukast decreased versus increased ICAM-1 expression in airway epithelial cells and HUVEC, respectively. For conclusions, bronchial surface epithelial and submucosal cells exhibit a different sensitivity profile toward dexamethasone, budesonide, and montelukast, with corticosteroids preventing cytokineinduced desmosomal damage in 16HBE cells. The studied drugs led to increased ICAM-1 expression in endothelium, potentially facilitating inflammatory cell migration into lung tissue.
Primary ciliary dyskinesia (PCD) is an autosomal recessive disease with extensive genetic heterogeneity. Dyskinetic or completely absent motility of cilia predisposes to recurrent pulmonary and upper respiratory tract infections resulting in bronchiectasis. Also infections of the middle ear are common due to lack of ciliary movement in the Eustachian tube. Men have reduced fertility due to spermatozoa with absent motility or abnormalities in the ductuli efferentes. Female subfertility and tendency to ectopic pregnancy has also been suggested. Headache, a common complaint in PCD patients, has been associated with absence of cilia in the brain ventricles, leading to decreased circulation of the cerebrospinal fluid. Finally, half of the patients with PCD has situs inversus, probably due to the absence of ciliary motility in Hensen's node in the embryo, which is responsible for the unidirectional flow of fluid on the back of the embryo, which determines sidedness. PCD, which is an inborn disease, should be distinguished from secondary ciliary dyskinesia (SCD) which is an acquired disease. Transmission electron microscopy is the most commonly used method for diagnosis of PCD, even though alternative methods, such as determination of ciliary motility and measurement of exhaled nitric oxide (NO) may be considered. The best method to distinguish PCD from SCD is the determination
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.