Effects of vitamin D on airway epithelial cell morphology and rhinovirus replication.
Vitamin D has been linked to reduced risk of viral respiratory illness. We hypothesized that vitamin D could directly reduce rhinovirus (RV) replication in airway epithelium. Primary human bronchial epithelial cells (hBEC) were treated with vitamin D, and RV replication and gene expression were evaluated by quantitative PCR. Cytokine/chemokine secretion was measured by ELISA, and transepithelial resistance (TER) was determined using a voltohmmeter. Morphology was examined using immunohistochemistry. Vitamin D supplementation had no significant effects on RV replication, but potentiated secretion of CXCL8 and CXCL10 from infected or uninfected cells. Treatment with vitamin D in the form of 1,25(OH)2D caused significant changes in cell morphology, including thickening of the cell layers (median of 46.5 µm [35.0-69.0] vs. 30 µm [24.5-34.2], p<0.01) and proliferation of cytokeratin-5-expressing cells, as demonstrated by immunohistochemical analysis. Similar effects were seen for 25(OH)D. In addition to altering morphology, higher concentrations of vitamin D significantly upregulated small proline-rich protein (SPRR1β) expression (6.3 fold-induction, p<0.01), suggestive of squamous metaplasia. Vitamin D treatment of hBECs did not alter repair of mechanically induced wounds. Collectively, these findings indicate that vitamin D does not directly affect RV replication in airway epithelial cells, but can influence chemokine synthesis and alters the growth and differentiation of airway epithelial cells.
Department of Pediatrics and Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
Rebecca A
RA
Brockman-Schneider
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America.
Raymond J
RJ
Pickles
Department of Pediatrics and Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
James E
JE
Gern
D001980:Bronchi / Q000187:drug effects / Q000473:pathology / Q000821:virology; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000378:metabolism; D055233:Cornified Envelope Proline-Rich Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure / Q000821:virology; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D053555:Keratin-5 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology / Q000821:virology; D012229:Rhinovirus / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects
C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054357:Chemokine CXCL10; D055233:Cornified Envelope Proline-Rich Proteins; D016209:Interleukin-8; D053555:Keratin-5; C524533:SPRR1B protein, human; D002117:Calcitriol