Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense.
The role of vitamin D in innate immunity is increasingly recognized. Recent work has identified a number of tissues that express the enzyme 1alpha-hydroxylase and are able to activate vitamin D. This locally produced vitamin D is believed to have important immunomodulatory effects. In this paper, we show that primary lung epithelial cells express high baseline levels of activating 1alpha-hydroxylase and low levels of inactivating 24-hydroxylase. The result of this enzyme expression is that airway epithelial cells constitutively convert inactive 25-dihydroxyvitamin D(3) to the active 1,25-dihydroxyvitamin D(3). Active vitamin D that is generated by lung epithelium leads to increased expression of vitamin D-regulated genes with important innate immune functions. These include the cathelicidin antimicrobial peptide gene and the TLR coreceptor CD14. dsRNA increases the expression of 1alpha-hydroxylase, augments the production of active vitamin D, and synergizes with vitamin D to increase expression of cathelicidin. In contrast to induction of the antimicrobial peptide, vitamin D attenuates dsRNA-induced expression of the NF-kappaB-driven gene IL-8. We conclude that primary epithelial cells generate active vitamin D, which then influences the expression of vitamin D-driven genes that play a major role in host defense. Furthermore, the presence of vitamin D alters induction of antimicrobial peptides and inflammatory cytokines in response to viruses. These observations suggest a novel mechanism by which local conversion of inactive to active vitamin D alters immune function in the lung.
Hansdottir
Sif
S
Department of Medicine, University of Iowa Carver College of Medicine, and Veterans Administration Medical Center, Iowa City, IA 52242, USA. sif-hansdottir@uiowa.edu
Monick
Martha M
MM
Hinde
Sara L
SL
Lovan
Nina
N
Look
Dwight C
DC
Hunninghake
Gary W
GW
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D007369:Interferon Inducers / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014807:Vitamin D / Q000378:metabolism*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D007369:Interferon Inducers; D018950:Lipopolysaccharide Receptors; D014807:Vitamin D; D011070:Poly I-C; D054804:Cathelicidins