Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice
| Autor: | Nele Heulens, Conny Gysemans, Chantal Mathieu, Karen Maes, Hannelie Korf, Erik Verbeken, Wim Janssens, Elien De Smidt, Ghislaine Gayan-Ramirez, Nele Cielen |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Time Factors Inflammation vitamin D deficiency Proinflammatory cytokine Pulmonary Disease Chronic Obstructive Phagocytosis Risk Factors Matrix Metalloproteinase 12 Smoke Parenchyma Macrophages Alveolar medicine Vitamin D and neurology Animals Vitamin D Lung Respiratory Burst COPD medicine.diagnostic_test business.industry Research Smoking Pneumonia respiratory system Macrophage Activation medicine.disease Vitamin D Deficiency respiratory tract diseases Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Bronchoalveolar lavage Pulmonary Emphysema Immunology Disease Progression Cytokines Calcium Female medicine.symptom Inflammation Mediators business Bronchoalveolar Lavage Fluid |
| Zdroj: | Respiratory Research |
| ISSN: | 1465-993X 1465-9921 |
| Popis: | Background Chronic obstructive pulmonary disease (COPD) is characterized by excessive inflammation and disturbed bacterial clearance in the airways. Although cigarette smoke (CS) exposure poses a major risk, vitamin D deficiency could potentially contribute to COPD progression. Many in vitro studies demonstrate important anti-inflammatory and antibacterial effects of vitamin D, but a direct contribution of vitamin D deficiency to COPD onset and disease progression has not been explored. Methods In the current study, we used a murine experimental model to investigate the combined effect of vitamin D deficiency and CS exposure on the development of COPD-like characteristics. Therefore, vitamin D deficient or control mice were exposed to CS or ambient air for a period of 6 (subacute) or 12 weeks (chronic). Besides lung function and structure measurements, we performed an in depth analysis of the size and composition of the cellular infiltrate in the airways and lung parenchyma and tested the ex vivo phagocytic and oxidative burst capacity of alveolar macrophages. Results Vitamin D deficient mice exhibited an accelerated lung function decline following CS exposure compared to control mice. Furthermore, early signs of emphysema were only observed in CS-exposed vitamin D deficient mice, which was accompanied by elevated levels of MMP-12 in the lung. Vitamin D deficient mice showed exacerbated infiltration of inflammatory cells in the airways and lung parenchyma after both subacute and chronic CS exposure compared to control mice. Furthermore, elevated levels of typical proinflammatory cytokines and chemokines could be detected in the bronchoalveolar lavage fluid (KC and TNF-α) and lung tissue (IP-10, MCP-1, IL-12) of CS-exposed vitamin D deficient mice compared to control mice. Finally, although CS greatly impaired the ex vivo phagocytic and oxidative burst function of alveolar macrophages, vitamin D deficient mice did not feature an additional defect. Conclusions Our data demonstrate that vitamin D deficiency both accelerates and aggravates the development of characteristic disease features of COPD. As vitamin D deficiency is highly prevalent, large randomized trials exploring effects of vitamin D supplementation on lung function decline and COPD onset are needed. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0271-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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