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

2007; Elsevier BV; Volume: 6; Issue: 6 Linguagem: Inglês

10.1016/j.jcf.2007.03.003

1873-5010

Sunghan Yim, Puneet Dhawan, Chandran Ragunath, Sylvia Christakos, Gill Diamond,

Insects and Parasite Interactions

BackgroundAntimicrobial 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 D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates AMP gene expression in several established cell lines. Furthermore, serum levels of vitamin D are often deficient in cystic fibrosis (CF) patients.MethodsWe investigated the effect of 1,25(OH)2D3 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.ResultsTreatment of NHBE cells with 1,25(OH)2D3 (10-8M), resulted in a 10-fold up-regulation of cathelicidin mRNA levels after 12 h, which was augmented 2-fold with co-incubation of 1 mM Calcium. Moreover, 1,25(OH)2D3 induced antimicrobial activity against the airway pathogens Bordetella bronchiseptica and Pseudomonas aeruginosa. 1,25(OH)2D3 induced cathelicidin mRNA expression equally in both normal and CF bronchial epithelial cells.ConclusionsElucidation of the effect of 1,25(OH)2D3 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.