%0 Journal Article %A Xingqi Wang %A Amy Nelson %A Anna Miller-Larsson %A Elisabet Wieslander %A Xiangde Liu %A Stephen Rennard %T HDAC2-independent anti-inflammatory effects of budesonide in human lung fibroblasts %D 2011 %J European Respiratory Journal %P p427 %V 38 %N Suppl 55 %X Background: Reduced response of COPD patients to the anti-inflammatory therapy with glucocorticoids may be due to reduced expression of histone deacetylase (HDAC) in alveolar macrophages and bronchial epithelial cells as suggested by recent studies. Lung fibroblasts release inflammatory mediators and are key cells in tissue remodeling following airway inflammation. However, HDAC expression and its role in mediating glucocorticoid effect on fibroblast functions have not been studied.Methods and results: Human fetal lung fibroblasts (HFL-1) were exposed to IL-1β +TNF-α (1ng/ml each), which stimulated release of IL-6, IL-8 and metalloproteinases MMP-1 and MMP-3. These responses were inhibited by the glucocorticoid budesonide (0.1-100nM) in a concentration-dependent manner. An HDAC inhibitor (trichostatin A) did not reverse the effects of budesonide on release of cytokines and MMPs in HFL-1 cells while it blocked the inhibitory effects of budesonide in human bronchial epithelial cells and monocytes. Furthermore, siRNA targeting HDAC2 did not interfere with the inhibitory effects of budesonide on HFL-1 MMP release. Exposure to cigarette smoke extract (5%) did not affect HDAC2 protein expression in HFL-1 cells and did not interfere with the budesonide effects. Finally, there was no statistically significant difference between COPD and control subjects in HDAC2 expression and the effects of budesonide on cytokine or MMP release from lung fibroblasts.Conclusions: HDAC2 is not required for budesonide to inhibit MMP and cytokine release by lung fibroblasts. These results also suggest that budesonide has a potential to counteract fibroblast-mediated tissue remodeling following airway inflammation in COPD. %U