Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D3

Background: Antimicrobial peptides (AMPs) such as cathelicidins contribute to initial defense of the airway against inhaled pathogens. Recent studies have shown that the hormonally active form of vitamin D-3, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) up-regulates AMP gene expression in several established cell lines. Furthenmore, serum levels of vitamin D are often deficient in cystic fibrosis (CF) patients. Methods: We investigated the effect of 1,25(OH)(2)D-3 on AMP mRNA levels in primary cultures of normal human bronchial epithelial (NHBE) cells by real-time PCR, and protein levels by Western blot. Antimicrobial activity of airway surface fluid from these cells was measured by in vitro assay against laboratory strains of bacteria. Results: Treatment of NHBE cells with 1,25(OH)(2)D-3 (10(-8)M), resulted in a 10-fold up-regulation of cathelicidin mRNA levels after 12 It, which was augmented 2-fold with co-incubation of I mM Calcium. Moreover, 1,25(OH)(2)D-3 induced antimicrobial activity against the airway pathogens Bordetella bronchiseptica and Pseudomonas aeruginosa. 1,25(OH)(2)D-3 induced cathelicidin mRNA expression equally in both normal and CF bronchial epithelial cells. Conclusions: Elucidation of the effect of 1,25(OH)(2)D-3 on cathelicidin expression in NHBE cells and CF bronchial epithelial cells will aid in the development of novel therapeutic agents for treatment of airway infections in CF. (c) 2007 European Cystic Fibrosis Society. Published by Elsevier B.V All rights reserved.