TY - JOUR T1 - Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium JF - European Respiratory Journal JO - Eur Respir J SP - 361 LP - 370 DO - 10.1183/09031936.00209513 VL - 44 IS - 2 AU - G. Jan Zijlstra AU - Fatemeh Fattahi AU - Dennie Rozeveld AU - Marnix R. Jonker AU - Nathalie M. Kliphuis AU - Maarten van den Berge AU - Machteld N. Hylkema AU - Nick H.T. ten Hacken AU - Antoon J.M. van Oosterhout AU - Irene H. Heijink Y1 - 2014/08/01 UR - http://erj.ersjournals.com/content/44/2/361.abstract N2 - Th17-mediated neutrophilic airway inflammation has been implicated in decreased response to glucocorticoids in asthma. We aimed to investigate the effect of glucocorticoids on the airway epithelial release of the neutrophilic and Th17-cell chemoattractant CCL20. We studied CCL20 and CXCL8 sputum levels in asthmatic subjects using inhaled glucocorticoids or not, and the effect of budesonide on CCL20 and CXCL8 production in primary bronchial epithelial cells. The mechanism behind the effect of budesonide-induced CCL20 production was studied in 16HBE14o- cells using inhibitors for the glucocorticoid receptor, intracellular pathways and metalloproteases. We observed higher levels of CCL20, but not CXCL8, in the sputum of asthmatics who used inhaled glucocorticoids. CCL20 levels correlated with inhaled glucocorticoid dose and sputum neutrophils. Budesonide increased tumour necrosis factor (TNF)-α-induced CCL20 by primary bronchial epithelium, while CXCL8 was suppressed. In 16HBE14o- cells, similar effects were observed at the CCL20 protein and mRNA levels, indicating transcriptional regulation. Although TNF-α-induced CCL20 release was dependent on the ERK, p38 and STAT3 pathways, the increase by budesonide was not. Inhibition of glucocorticoid receptor or ADAM17 abrogated the budesonide-induced increase in CCL20 levels. We show that glucocorticoids enhance CCL20 production by bronchial epithelium, which may constitute a novel mechanism in Th17-mediated glucocorticoid-insensitive inflammation in asthma. Glucocorticoids enhance production of CCL20 by airway epithelial cells: a mechanism of inflammation in asthma? http://ow.ly/tyzt1 ER -