RT Journal Article
SR Electronic
T1 Differential effects of simvastatin and dexamethasone on TLR3-induced anti-viral cytokines in asthmatic epithelium
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3145
VO 42
IS Suppl 57
A1 Angelica Brandelius
A1 Irma Mahmutovic Persson
A1 Jenny Calvén
A1 Leif Bjermer
A1 Carl Persson
A1 Morgan Andersson
A1 Lena Uller
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P3145.abstract
AB Possibly reflecting anti-inflammatory properties, statin treatment may ameliorate viral-induced exacerbations. We have shown that simvastatin but not dexamethasone inhibits viral-induced, potentially pathogenic thymic stromal lymphopoietin production. It is important that treatments of exacerbations spare the host defence to viral infections. IFN-beta, IFN-lambda and IL-32 are major antiviral components of innate immunity.Objective: Explore effects of simvastatin and dexamethasone on TLR3-induced IFN-beta, IFN-lambda and IL-32 in asthmatic epithelium.Methods: Primary bronchial epithelial cells, obtained by fibre optic bronchoscopy from allergic asthma patients (n=6) were grown in 12-well plates and treated with simvastatin (0,2-5μg), dexamethasone (1μM) or vehicle control prior to TLR3 stimulation for 3 and 24 h and samples analysed by RTqPCR and ELISA.Results: TLR3 stimulation induced early (3h) expression of IFN-beta (1000-fold) that was dose-dependently inhibited by simvastatin but not by dexamethasone. IFN-lambda was induced (6000-fold) at 3h and further sustained at 24 h (2000-fold). Only the early IFN-lambda expression was reduced by the highest dose of simvastatin. Dexamethasone was without effect. IL-32 was induced (2-fold) at 3h and further increased at 24h. At both time-points the highest dose of simvastatin reduced IL-32 but dexamethasone was without effect.Conclusion: Dexamethasone treatment spared TLR3-induced expression of all three anti-viral cytokines in bronchial epithelial cells from asthma donors. Simvastatin completely inhibited TLR3-induced IFN-beta whereas the inducement of IFN-lambda and IL-32 were largely spared by simvastatin.