Department CHROMETA, Laboratory of Respiratory diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.
Clinical department of Respiratory Diseases, UZ Leuven, Campus Gasthuisberg, ON I Herestraat 49 - bus, 706 3000, Leuven, Belgium.
Respir Res. 2020 Jun 3;21(1):137. doi: 10.1186/s12931-020-01405-0.
Treatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D. However, little is known about local vitamin D metabolism in the airways and studies examining expression of the vitamin D receptor (VDR), the activating enzyme (CYP27B1) and inactivating enzyme (CYP24A1) of vitamin D in lung tissue of COPD patients are lacking. Therefore, the expression and localization of key enzymes and the receptor of the vitamin D pathway were examined in tissue of 10 unused donor lungs and 10 COPD explant lungs. No differences in the expression of CYP27B1 and CYP24A1 were found. Although protein expression of VDR was significantly lower in COPD explant tissue, there was no difference in downstream expression of the antimicrobial peptide cathelicidin. Whereas CYP27B1 and CYP24A1 were present in all layers of the bronchial epithelium, VDR was only expressed at the apical layer of a fully differentiated bronchial epithelium with no expression in vascular endothelial cells. By contrast, CYP24A1 expression was highly present in lung endothelial cells suggesting that systemic vitamin D can be inactivated before reaching the epithelial compartment and the tissue immune cells. These data support the idea of exploring the role of vitamin D inhalation in patients with COPD.
慢性阻塞性肺疾病（COPD）的治疗基于支气管扩张，当频繁发生恶化时，联合吸入皮质类固醇或阿奇霉素。尽管当前治疗方案的益处已得到证实，但在明确的亚组中仍需要新的干预措施。有确凿的证据表明，口服维生素 D 补充剂可减少严重缺乏循环维生素 D 的 COPD 患者的恶化。然而，对于气道中局部维生素 D 代谢知之甚少，并且缺乏研究检查 COPD 患者肺组织中维生素 D 受体（VDR）、激活酶（CYP27B1）和失活酶（CYP24A1）的表达。因此，在 10 个未使用的供体肺组织和 10 个 COPD 肺组织中检查了维生素 D 途径的关键酶和受体的表达和定位。未发现 CYP27B1 和 CYP24A1 的表达存在差异。尽管 COPD 肺组织中的 VDR 蛋白表达明显降低，但抗菌肽 cathelicidin 的下游表达没有差异。虽然 CYP27B1 和 CYP24A1 存在于支气管上皮的所有层中，但 VDR 仅在上皮细胞的顶端层表达，而在血管内皮细胞中不表达。相比之下，CYP24A1 的表达在肺内皮细胞中高度存在，表明系统维生素 D 可以在到达上皮细胞室和组织免疫细胞之前失活。这些数据支持探索 COPD 患者吸入维生素 D 作用的想法。
