Vitamin D deficiency; Acute lung inflammation; Local vitamin D nebulization
Abstract :
[en] Background: Evidence supports a critical role of vitamin D status on exacerbation in chronic obstructive pulmonary disease, indicating the need to avoid vitamin D deficiency in these patients. However, oral vitamin D supplementation is limited by the potential risk for hypercalcemia. In this study, we investigated if local delivery of vitamin D to the lungs improves vitamin D-mediated anti-inflammatory action in response to acute inflammation without inducing hypercalcemia. Methods: We studied vitamin D sufficient (VDS) or deficient (VDD) mice in whom 1α,25(OH) 2 D 3 (0.2 μg/kg) or a vehicle followed by lipopolysaccharide (LPS 25 µg) were delivered to the lung as a micro-spray. Results: Local 1α,25(OH) 2 D 3 reduced LPS-induced inflammatory cells in bronchoalveolar lavage (BAL) in VDS (absolute number of cells: − 57% and neutrophils − 51% p < 0.01) and tended to diminish LPS-increased CXCL5 BAL levels in VDS (− 40%, p = 0.05) while it had no effect on CXCL1 and CXCL2 in BAL and mRNA in lung of VDS and VDD. It also significantly attenuated the increased IL-13 in BAL and lung, especially in VDD mice (− 41 and − 75%, respectively). mRNA expression of Claudin-18 in lung was significantly lower in VDS mice with local 1α,25(OH) 2 D 3 while Claudin-3,-5 and-8 mRNA levels remained unchanged. Finally, in VDD mice only, LPS reduced lung mRNA expression of adhesion junction Zona-occludens-1, in addition to increasing uric acid and total protein in BAL, which both were prevented by local 1α,25(OH) 2 D 3. Conclusion: Under normal levels of vitamin D, local 1α,25(OH) 2 D 3 nebulization into the lung efficiently reduced LPS induction of inflammatory cells in BAL and slightly attenuated LPS-increase in CXCL5. In case of severe vitamin D deficiency, although local 1α,25(OH) 2 D 3 nebulization failed to significantly minimize cellular inflammation in BAL at this dose, it prevented epithelial barrier leakage and damage in lung. Additional research is needed to determine the potential long-term beneficial effects of local 1α,25(OH)2D3 nebulization on lung inflammation.
Research center :
GIGA-LBTD - GIGA Cancer-Tumours and development biology - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Serré, Jef; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium
Mathyssen, Carolien; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium
Ajime, Tom; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium
Heigl, Tobias; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium
Verlinden, Lieve; Clinical and Experi-mental Endocrinology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
Maes, Karen; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium
Verstuyf, Annemieke; Clinical and Experi-mental Endocrinology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
Cataldo, Didier ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Vanoirbeek, Jeroen; Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Leuven, Belgium
Vanaudenaerde, Bart; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium
Janssens, Wim; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Clinical Department of Res-piratory Diseases, UZ Leuven, Leuven, Belgium
Gayan-Ramirez, Ghislaine ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium ; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven ; O&NI bis, Leuven, Belgium
Language :
English
Title :
Local nebulization of 1α,25(OH) 2 D 3 attenuates LPS-induced acute lung inflammation
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