Abstract
Although inhaled corticosteroids reduce the number of exacerbations in COPD, it has been established that fluticasone propionate(FP) increases the risk of pneumonia, a finding not reported or in lower frequency with budesonide (BUD). The mechanisms underlying this difference are unknown. We hypothesized that FP is more efficacious than BUD in the suppression of immune defense genes upon viral infection. Methods: Primary bronchial epithelial cells from healthy donors (n=11) were cultured for 4 weeks at air-liquid interface to induce mucociliary differentiation. Cells were pre-treated for 2 h with equivalent concentrations of FP (10 nM) or BUD (16 nM) and exposed to rhinovirus (RV) for 24 h. The mRNA expression of antimicrobial defense genes RIG-I, INF-β, S100A8 and lactoferrin, and epithelial barrier molecule E-cadherin, was assessed by qPCR. Results: Exposure to RV significantly increased the expression of RIG-I, IFN-β and S100A8, but not of lactoferrin or E-cadherin. In RV-exposed epithelium, FP and BUD significantly and similarly reduced RIG-I expression, but had no effect on IFN-β, S100A8 or lactoferrin. Interestingly, E-cadherin expression was only reduced by FP (p=0.03), and E-cadherin, S100A8 and lactoferrin expression was significantly higher upon RV+BUD than RV+FP treatment (p<0.05). Conclusions: Pre-treatment of RV-exposed human bronchial epithelium with BUD results in significantly higher expression of S100A8, lactoferrin and E-cadherin than that with FP. The differential regulation of these immune defense genes may help to explain the putative difference between FP and BUD with respect to the risk to develop pneumonia. Supported by AstraZeneca.
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