Vitamin D attenuates rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PAFR) in respiratory epithelial cells

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 187; pp. 152 - 159
• Main Authors: Greiller, Claire L., Suri, Reetika, Jolliffe, David A., Kebadze, Tatiana, Hirsman, Aurica G., Griffiths, Christopher J., Johnston, Sebastian L., Martineau, Adrian R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2019; Elsevier BV
• Subjects: 1,25-dihydroxyvitamin D; 25-Hydroxyvitamin D; A549 Cells; Antimicrobial peptides; Bacterial infections; Calcitriol - pharmacology; CAMP; Cell adhesion; Cell surface; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - virology; G protein-coupled receptors; Gene Expression Regulation - drug effects; Host-Parasite Interactions - drug effects; Human rhinovirus; Humans; ICAM1; IKBA; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - genetics; NF-κB protein; Picornaviridae Infections - genetics; Picornaviridae Infections - prevention & control; Platelet Membrane Glycoproteins - genetics; Platelet-activating factor; PTAFR; Receptors, G-Protein-Coupled - genetics; Respiratory epithelial cells; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Respiratory Mucosa - virology; Rhinovirus; Rhinovirus - drug effects; Rhinovirus - physiology; Streptococcus infections; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - pharmacology; Vitamins - pharmacology; IKBA; 25-hydroxyvitamin D; Respiratory epithelial cells; 1,25-dihydroxyvitamin D; PTAFR; Human rhinovirus; CAMP; ICAM1
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2018.11.013

•25-hydroxyvitamin D attenuated rhinovirus-induced expression of ICAM-1 and PTAFR in a respiratory epithelial cell line.•These effects were associated with enhanced expression of the genes encoding the NF-κB inhibitor IκBα and the antimicrobial peptide cathelicidin LL-37.•Our findings suggest possible mechanisms by which vitamin D may enhance resistance to rhinovirus infection and reduce risk of secondary bacterial infection in vitamin D-deficient individuals. Human rhinoviruses commonly cause upper respiratory infections, which may be complicated by secondary bacterial infection. Vitamin D replacement reduces risk of acute respiratory infections in vitamin D-deficient individuals, but the mechanisms by which such protection is mediated are incompletely understood. We therefore conducted experiments to characterise the influence of the major circulating metabolite 25-hydroxyvitamin D (25[OH]D) and the active metabolite 1,25-dihydroxyvitamin D (1,25[OH]2D) on responses of a respiratory epithelial cell line (A549 cells) to infection with a major group human rhinovirus (RV-16). Pre-treatment of A549 respiratory epithelial cells with a physiological concentration (10−7M) of 25(OH)D induced transient resistance to infection with RV-16 and attenuated RV-16-induced expression of the genes encoding intercellular adhesion molecule 1 (ICAM-1, a cell surface glycoprotein that acts as the cellular receptor for major group rhinoviruses) and platelet-activating factor receptor (PAFR, a G-protein coupled receptor implicated in adhesion of Streptococcus pneumoniae to respiratory epithelial cells). These effects were associated with enhanced expression of the genes encoding the NF-κB inhibitor IκBα and the antimicrobial peptide cathelicidin LL-37. Our findings suggest possible mechanisms by which vitamin D may enhance resistance to rhinovirus infection and reduce risk of secondary bacterial infection in vitamin D-deficient individuals.