Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial

Abstract


 
 
 
 Background: Vitamin D deficiency has been implicated as a factor in a number of infectious and inflammatory lung diseases. In the lung, alveolar macrophages play a key role in inflammation and defense of infection, but there are little data exploring the immunomodulatory effects of vitamin D on innate lung immunity in humans. The objective of this study was to determine the effects of vitamin D supplementation on gene expression of alveolar macrophages.
 Methods: We performed a parallel, double-blind, placebo-controlled, randomized trial to determine the effects of vitamin D on alveolar macrophage gene expression. Vitamin D3 (1000 international units/day) or placebo was administered to adults for three months. Bronchoscopy was performed pre- and post-intervention to obtain alveolar macrophages. Messenger RNA was isolated from the macrophages and subjected to whole genome exon array analysis. The primary outcome was differential gene expression of the alveolar macrophage in response to vitamin D supplementation. Specific genes underwent validation by polymerase chain reaction methods.
 Results: Fifty-eight subjects were randomized to vitamin D (n = 28) or placebo (n = 30). There was a marginal overall difference between treatment group and placebo group in the change of 25-hydroxyvitaminD levels(4.43 ng/ml vs. 0.2 ng/ml, p = 0.10). Whole genome exon array analysis revealed differential gene expression associated with change in serum vitamin D levels in the treated group. CCL8/MCP-2 was the top-regulated cytokine gene and was further validated.
 Conclusions: Although only a non-significant increased trend was seen in serum vitamin D levels, subjects treated with vitamin D supplementation had immune-related differential gene expression in alveolar macrophages.
 Trial registration: ClinicalTrials.org: NCT01967628.
 
 
 

Vitamin D supplementation and immune-related markers: an update from nutrigenetic and nutrigenomic studies

“…In HIV-infected patients, a high-dose cholecalciferol (25 000 μg weekly) increased CCR10 gene expression levels and reduced CCR4 expression level of skin-homing markers, while a low dose (800 μg/d) failed to produce any immunomodulatory effects (52) . In contrast, 7000 μg of vitamin D 3 significantly increased CAMP expression after 52 weeks and promoted antibacterial immunity in HIV-positive adolescents and young adults (n 48) (66) . Supplementing 1000 μg/d did not find any significant changes in alveolar macrophage gene expression in a study on healthy US adults (n 28) (67) , while it increased airway surface liquid antimicrobial activity and gene expression of cathelicidin antimicrobial peptide in the same population (67) .…”

Vitamin D Deficiency: Implications in COVID-19 and Schizophrenia

“…Activation of VDR in the epithelium stimulates production of several anti-microbial proteins that hinder the entrance of such pathogens. Concurrently, VDR activation in lung macrophages is thought to prevent immune system hyperactivity by way of decreasing inflammatory signals [48].…”

Ebola virus

“…RNA preparation, quality analysis and microarray analysis were performed as previously described (277). Microarrays assessed genome-wide macrophage mRNA expression using the GeneChip Human Exon 1.0 ST Arrays (Affymetrix).…”

“…Six of the top genes identified in the MDM and alveolar macrophage microarray analysis were validated by qRT-PCR as described above and previously described (277).…”