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Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice.
Respir Res 2015; 16:110RR

Abstract

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.

Authors+Show Affiliations

Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. nele.heulens@med.kuleuven.be.Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. hannelie.korf@med.kuleuven.be.Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. nele.cielen@med.kuleuven.be.Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. elien.desmidt@med.kuleuven.be.Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. karen.maes@med.kuleuven.be.Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. conny.gysemans@med.kuleuven.be.Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, Minderbroederstraat 12, 3000, Leuven, Belgium. eric.verbeken@uzleuven.be.Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. ghislaine.gayan-ramirez@med.kuleuven.be.Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. chantal.mathieu@uzleuven.be.Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. wim.janssens@uzleuven.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26376849

Citation

Heulens, Nele, et al. "Vitamin D Deficiency Exacerbates COPD-like Characteristics in the Lungs of Cigarette Smoke-exposed Mice." Respiratory Research, vol. 16, 2015, p. 110.
Heulens N, Korf H, Cielen N, et al. Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice. Respir Res. 2015;16:110.
Heulens, N., Korf, H., Cielen, N., De Smidt, E., Maes, K., Gysemans, C., ... Janssens, W. (2015). Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice. Respiratory Research, 16, p. 110. doi:10.1186/s12931-015-0271-x.
Heulens N, et al. Vitamin D Deficiency Exacerbates COPD-like Characteristics in the Lungs of Cigarette Smoke-exposed Mice. Respir Res. 2015 Sep 16;16:110. PubMed PMID: 26376849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice. AU - Heulens,Nele, AU - Korf,Hannelie, AU - Cielen,Nele, AU - De Smidt,Elien, AU - Maes,Karen, AU - Gysemans,Conny, AU - Verbeken,Erik, AU - Gayan-Ramirez,Ghislaine, AU - Mathieu,Chantal, AU - Janssens,Wim, Y1 - 2015/09/16/ PY - 2015/05/19/received PY - 2015/08/30/accepted PY - 2015/9/18/entrez PY - 2015/9/18/pubmed PY - 2016/7/13/medline SP - 110 EP - 110 JF - Respiratory research JO - Respir. Res. VL - 16 N2 - 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. SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/26376849/Vitamin_D_deficiency_exacerbates_COPD_like_characteristics_in_the_lungs_of_cigarette_smoke_exposed_mice_ L2 - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-015-0271-x DB - PRIME DP - Unbound Medicine ER -