Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism
| Autor: | William W. Carroll, Carl Atkinson, Whitney N. Pasquini, Jennifer K. Mulligan, Rodney J. Schlosser, Nicholas Reaves, Tucker Williamson, Kunal Patel, Elliott Mappus |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neutrophils Physiology lcsh:Medicine Pathology and Laboratory Medicine T-Lymphocytes Regulatory Mice White Blood Cells chemistry.chemical_compound 0302 clinical medicine Animal Cells Immune Physiology Medicine and Health Sciences Nasal polyps Lymphocytes lcsh:Science 030223 otorhinolaryngology Immune Response Cholecalciferol Rhinitis Innate Immune System Multidisciplinary T Cells Nutritional Deficiencies Animal Models respiratory system 3. Good health medicine.anatomical_structure Experimental Organism Systems Micronutrient Deficiencies Cytokines Cellular Types medicine.symptom Research Article Vitamin Immune Cells Inflammatory Diseases Immunology Mouse Models Inflammation Research and Analysis Methods vitamin D deficiency Immune Deficiency 03 medical and health sciences Nasal Polyps Model Organisms Signs and Symptoms Immune system Diagnostic Medicine otorhinolaryngologic diseases medicine Animals Humans Sinusitis Nutrition Blood Cells business.industry Aspergillus fumigatus lcsh:R Biology and Life Sciences Cell Biology Molecular Development Eosinophil Vitamin D Deficiency medicine.disease Blood Cell Count Diet Eosinophils Disease Models Animal 030104 developmental biology chemistry Immune System Dietary Supplements Nasal Lavage lcsh:Q Clinical Immunology Nasal administration Clinical Medicine business Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 10, p e0186374 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0186374 |
| Popis: | Rationale Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Methods Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Results Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. Conclusions VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|