Abstract book 2011 - ISHAM

ASPERGILLUS-INDUCED INFLAMMATION IN THE CYSTIC FIBROSISLUNG: RESPONSE TO ANTIFUNGAL THERAPY.Sanjay Chotirmall, Catherine A. Coughlin, Emer P. Reeves, Philip Murphy, JulieRenwick, Cedric Gunaratnam and Noel Gerard McElvaneyRCSI, Beaumont Hospital, Dublin, IrelandIn this study, we show that vitamin D receptor (VDR) gene expression was significantly downregulated by Aspergillus culture media in CFTE and CFBE cells. qRT-PCR confirmedsignificant down regulation of VDR gene expression in vivo in bronchial brushings fromAspergillus colonised patients in line with in vitro results. The VDR modulator present withinculture filtrates of A. fumigatus was characterized. The inhibitory activity was stable withincultures stored at -70°C and subsequently used against CFBE cells at 37°C but wassignificantly abolished by heat inactivation (99°C) for 20 min. Passage of culture filtratesthrough a 3 kDa size exclusion filter removed approximately 65% of the VDR inhibitoryactivity, and this was recovered in the filtrate, which suggested the presence of both high- butpredominately low-molecular weight (