PURPOSE:Corticosteroids, the first line treatment for asthma patients, are known to act via their pro-apoptotic effect on inflammatory cells. However, their effect on constitutive airway cells is less clear. We examined epithelial desmosomes and ICAM expression in cultured airway epithelial cells and primary endothelial cells before and after treatment with corticosteroids and montelukast.
METHODS:The cell line 16HBE, is a human airway epithelial cell line transformed with simian vacuolating virus 40 that has cell surface markers similar to primary airway surface epithelial cells. HUVEC is human umbilical vein cells. Monoclonal mouse anti-human ICAM-1 (CD54) antibody was used to detect ICAM-1 in 16HBE and HUVEC cells analyzed in a FACSCalibur fluorescence-activated cell sorter. 5000 cells were analyzed per each sample. TEM was used to quantify desmosomes in cell cultures treated with cytokines or cytokines plus corticosteroids. A total of 100 μm lateral cell membrane per sample was measured, and the relative length occupied by desmosomes was determined.
RESULTS:Dexamethasone, beclomethasone and montelukast increased the level of ICAM-1 expression in HUVEC cells, while budesonide was without effect (Fig. 1). The effect of corticosteroids and montelukast in epithelial cells (16HBE) was the opposite of that in endothelial cells: all drugs led to decreased amount of ICAM-1 (Fig. 2). Desmosomal length was decreased in the presence of cytokines (TNF-α and INF-γ) with corticosteroids counteracting this reduction (Fig. 3).
CONCLUSION:Epithelial and endothelial cells demonstrate a different pattern of ICAM-1 expression after exposure to corticosteroids and montelukast. Corticosteroids shown to counteract cytokine damage to desmosomes.
CLINICAL IMPLICATIONS:The finding needs to be explored further to better understand the pathophysiologic effect of the treatment administered in asthma. Corticosteroids seem to offer protection against cytokine damage to airway epithelium.
DISCLOSURE:Zhanna Servetnyk, No Financial Disclosure Information; No Product/Research Disclosure Information