The Second Affiliated Hospital, Anhui Medical University, Hefei 230032, China.
Department of Toxicology, Anhui Medical University, Hefei 230032, China; and.
J Immunol. 2021 Feb 1;206(3):515-523. doi: 10.4049/jimmunol.2000964. Epub 2020 Dec 23.
Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1-2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)D inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)D reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.
维生素 D 缺乏与慢性阻塞性肺疾病(COPD)的风险增加有关。然而,其机制尚不清楚。本研究分析了维生素 D 水平与 COPD 患者炎症之间的相关性。共纳入 101 例 COPD 患者和 202 例对照者。检测血清 25(OH)D 水平和炎症细胞因子。COPD 患者的血清 25(OH)D 降低,炎症细胞因子增加。根据 1 秒用力呼气量(FEV1),将 COPD 患者分为三级。此外,COPD 患者的血清 25(OH)D 逐渐降低,从 1-2 级到 4 级。血清 25(OH)D 与 COPD 患者的炎症细胞因子呈负相关。进一步分析发现 COPD 患者中 NF-κB 和 AP-1 信号通路被激活。此外,炎症信号与 COPD 的严重程度平行逐渐增加。相比之下,COPD 患者的肺核维生素 D 受体减少。体外实验表明,1,25(OH)D 抑制了 LPS 激活的 A549 细胞(人肺腺癌细胞)中的炎症信号。从机制上讲,1,25(OH)D 增强了维生素 D 受体与 NF-κB p65 和 c-Jun 之间的物理相互作用。我们的结果表明,维生素 D 与 COPD 患者的炎症信号呈负相关。在维生素 D 水平较低的患者中,炎症可能是 COPD 进展的重要介质。