Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense.

Abstract

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.

5 Figures and Tables

0100200200920102011201220132014201520162017
Citations per Year

831 Citations

Semantic Scholar estimates that this publication has 831 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Hansdottir2008RespiratoryEC, title={Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense.}, author={Sif Hansdottir and Martha M. Monick and Sara L Hinde and Nina Lovan and Dwight C. Look and Gary W. Hunninghake}, journal={Journal of immunology}, year={2008}, volume={181 10}, pages={7090-9} }