Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro

Antiviral Res. 2017 Jan;137:93-101. doi: 10.1016/j.antiviral.2016.11.004. Epub 2016 Nov 10.

Abstract

Background: By modulating the antiviral immune response via vitamin D receptor, the active form of vitamin D (1,25-dihydroxyvitamin D, calcitriol) could play a central role in protection against respiratory virus infections. This in vitro study tested the hypothesis that respiratory viruses modulate vitamin D receptor expression in human bronchial epithelial cells and this modulation affects the antiviral response to exogenous vitamin D.

Methods: Human primary bronchial epithelial cells were infected with rhinoviruses and respiratory syncytial virus in the presence or absence of vitamin D. Expression of vitamin D receptor, 1α-hydroxylase (1α(OH)ase), 24-hydroxylase (24(OH)ase), innate interferons, interferon stimulated genes and cathelicidin were measured by quantitative polymerase chain reaction. The antiviral effect of vitamin D on rhinovirus replication was determined by measurement of virus load. A direct inactivation assay was used to determine the antiviral activity of cathelicidin.

Results: Both RV and RSV decreased vitamin D receptor and 24(OH)ase and, in addition, RSV increased 1α(OH)ase expression in epithelial cells. Vitamin D decreased rhinovirus replication and release, and increased rhinovirus-induced interferon stimulated genes and cathelicidin. Furthermore, cathelicidin had direct anti-rhinovirus activity.

Conclusions: Despite lower vitamin D receptor levels in rhinovirus-infected epithelial cells, exogenous vitamin D increased antiviral defences most likely via cathelicidin and innate interferon pathways.

Keywords: Cathelicidin; Interferons; Respiratory viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / genetics
  • Antiviral Agents / pharmacology*
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / virology*
  • Calcitriol / pharmacology*
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology*
  • Humans
  • Immunity, Innate
  • Interferons / immunology
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Syncytial Virus, Human / drug effects*
  • Rhinovirus / drug effects*
  • Vitamin D / chemistry
  • Vitamin D / pharmacology
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamin D3 24-Hydroxylase / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Antiviral Agents
  • Receptors, Calcitriol
  • Vitamin D
  • CAP18 lipopolysaccharide-binding protein
  • Interferons
  • Vitamin D3 24-Hydroxylase
  • Calcitriol