Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37

Eur Respir J. 2016 Feb;47(2):520-30. doi: 10.1183/13993003.00665-2015. Epub 2015 Nov 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antimicrobial Cationic Peptides
  • Bronchi / cytology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / virology
  • Case-Control Studies
  • Cathelicidins / drug effects*
  • Cathelicidins / metabolism
  • Child
  • Child, Preschool
  • Cholecalciferol / pharmacology*
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / virology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / virology
  • Female
  • Humans
  • Infant
  • Male
  • Real-Time Polymerase Chain Reaction
  • Rhinovirus / drug effects*
  • Viral Load
  • Virus Replication / drug effects*
  • Vitamin D / pharmacology
  • Vitamins / pharmacology*

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Vitamins
  • Vitamin D
  • Cholecalciferol