Respiratory Epithelial Cells Convert Inactive Vitamin D to Its Active Form: Potential Effects on Host Defense
Open Access
- 15 November 2008
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 181 (10), 7090-7099
- https://doi.org/10.4049/jimmunol.181.10.7090
Abstract
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.Keywords
This publication has 81 references indexed in Scilit:
- Histone Acetylation in Keratinocytes Enables Control of the Expression of Cathelicidin and CD14 by 1,25-Dihydroxyvitamin D3Journal of Investigative Dermatology, 2008
- Vitamin D DeficiencyThe New England Journal of Medicine, 2007
- Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancerThe Journal of Steroid Biochemistry and Molecular Biology, 2007
- Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanismJCI Insight, 2007
- Circulating 25-Hydroxyvitamin D Levels Predict Survival in Early-Stage Non–Small-Cell Lung Cancer PatientsJournal of Clinical Oncology, 2007
- DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27Nature Immunology, 2007
- Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial ResponseScience, 2006
- Calcium plus Vitamin D Supplementation and the Risk of Colorectal CancerThe New England Journal of Medicine, 2006
- Expression of 25-hydroxyvitamin D-1-α-hydroxylase mRNA in individuals with colorectal cancerThe Lancet, 2002
- When Two Strands Are Better Than One: The Mediators and Modulators of the Cellular Responses to Double-Stranded RNAVirology, 1996