title: Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37.
abstract: Vitamin D has immunomodulatory properties in the defence against pathogens. Its insufficiency is a widespread feature of cystic fibrosis (CF) patients, which are repeatedly suffering from rhinovirus (RV)-induced pulmonary exacerbations.To investigate whether vitamin D has antiviral activity, primary bronchial epithelial cells from CF children were pre-treated with vitamin D and infected with RV16. Antiviral and anti-inflammatory activity of vitamin D was assessed. RV and LL-37 levels were measured in bronchoalveolar lavage (BAL) of CF children infected with RV.Vitamin D reduced RV16 load in a dose-dependent manner in CF cells (10(-7 )M, p<0.01). The antiviral response mediated by interferons remained unchanged by vitamin D in CF cells. Vitamin D did not exert anti-inflammatory properties in RV-infected CF cells. Vitamin D increased the expression of the antimicrobial peptide LL-37 up to 17.4-fold (p<0.05). Addition of exogenous LL-37 decreased viral replication by 4.4-fold in CF cells (p<0.05). An inverse correlation between viral load and LL-37 levels in CF BAL (r=-0.48, p<0.05) was observed.RV replication in primary CF bronchial cells was reduced by vitamin D through the induction of LL-37. Clinical studies are needed to determine the importance of an adequate control of vitamin D for prevention of virus-induced pulmonary CF exacerbations.
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Bern, Switzerland Dept of Clinical Research, University of Bern, Bern, Switzerland Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Aline
authors.initials: A
authors.lastname: Schögler
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Bern, Switzerland Dept of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Muster
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Bern, Switzerland University Children`s Hospital Basel, UKBB, Basel, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kieninger
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Bern, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Casaulta
authors.affiliation: Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tapparel
authors.affiliation: Division of Respiratory Medicine, University Children's Hospital, Zürich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.affiliation: Division of Respiratory Medicine, University Children's Hospital, Zürich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Moeller
authors.affiliation: Dept of Clinical Research, University of Bern, Bern, Switzerland Dept of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geiser
authors.affiliation: Dept of Clinical Research, University of Bern, Bern, Switzerland Division of Paediatric Respiratory Medicine, Lucerne Children's Hospital, Lucerne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Regamey
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Bern, Switzerland Dept of Clinical Research, University of Bern, Bern, Switzerland marco.alves@dkf.unibe.ch.
authors.forename: Marco P
authors.initials: MP
authors.lastname: Alves
mesh_terms: D000293:Adolescent; D023181:Antimicrobial Cationic Peptides; D001980:Bronchi / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000821:virology; D016022:Case-Control Studies; D054804:Cathelicidins / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002762:Cholecalciferol / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000821:virology; D004847:Epithelial Cells / Q000187:drug effects* / Q000821:virology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D012229:Rhinovirus / Q000187:drug effects*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*; D014807:Vitamin D / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol