Respiratory Epithelial Cells Convert Inactive Vitamin D to its Active Form
By S. Hansdóttir, M. Monick, Sara L. Hinde, Nina Lovan, D. Look, G. Hunninghake. Journal of Immunology, 2008
615 citations recorded by the source corpus.
The role of vitamin D in innate immunity is increasingly recognized. Recent work has identified a number of tissues that express the enzyme 1α-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 1α-hydroxylase and low levels of inactivating 24-hydroxylase. The result of this enzyme expression is that airway epithelial cells constitutively convert inactive 25-dihydroxyvitamin D3 to the active 1,25-dihydroxyvitamin D3. 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 1α-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-κB-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.
Subfields: Endocrinology, Diabetes and Metabolism, Nutrition and Dietetics, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/852de2f934f7c7ba50951dad700f3ca551fc8d96
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Citations in the corpus
- Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data (2017, background): “3 4 25-hydroxyvitamin D supports induction of antimicrobial peptides in response to both viral and bacterial stimuli, 5-7 suggesting a potential mechanism by which vitamin D inducible protection against respiratory pathogens might be mediated.”
- “Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study” (2020, positive): “In addition, in a viral infection model, dsRNA leads to increased regulation of 1α-hydroxylase and synergizes with calcifediol and calcitriol sequentially to induce cathelicidin [34].”