Department of Allergy and Clinical Immunology, Keimyung University School of Medicine, Daegu, South Korea.
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
Clin Exp Allergy. 2023 Jun;53(6):648-658. doi: 10.1111/cea.14315. Epub 2023 Apr 3.
Club cell 16-kDa secretory protein (CC16) is a pneumoprotein and functions as an anti-inflammatory or antioxidant protein. However, altered levels of serum CC16 as well as their effect on airways inflammation have not been fully evaluated.
We recruited 63 adult asthmatics on maintenance medications and 61 healthy controls (HCs). The asthmatic subjects were divided into two groups according to the result of bronchodilator responsiveness (BDR) test: the present BDR (n = 17) and absent BDR (n = 46) groups. Serum CC16 levels were measured by ELISA. As an in vitro study, the effect of Dermatophagoides pteronyssinus antigen 1 (Der p1) on the production of CC16 in airways epithelial cells (AECs) according to a time-dependent manner was assessed; the effects of CC16 protein on oxidative stress system, airways inflammation and remodelling were tested.
Serum CC16 levels showed significantly higher in the asthmatics than in the HCs (p < .001) with a positive correlation with FEV % (r = .352, p = .005). The present BDR group had significantly lower levels of serum CC16, FEV % and MMEF%, but showed higher level of FeNO than the absent BDR group. Serum CC16 levels (below 496.0 ng/mL) could discriminate the present BDR group from the absent BDR group (area under the curve = 0.74, p = .004). In vitro testing demonstrated that Der p1 exposure significantly induced CC16 release from AECs for 1 h, which was progressively decreased after 6 h and followed by MMP-9 and TIMP-1 production. These findings were associated with oxidant/antioxidant disequilibrium and restored by CC16 treatment (but not dexamethasone).
Decreased CC16 production contributes to persistent airways inflammation and lung function decline. CC16 may be a potential biomarker for asthmatics with BDR.
克拉细胞 16kDa 分泌蛋白（CC16）是一种肺蛋白，具有抗炎或抗氧化作用。然而，血清 CC16 的水平变化及其对气道炎症的影响尚未得到充分评估。
我们招募了 63 名正在服用维持药物的成年哮喘患者和 61 名健康对照者（HCs）。根据支气管扩张剂反应性（BDR）测试的结果，将哮喘患者分为两组：有 BDR 组（n=17）和无 BDR 组（n=46）。通过 ELISA 法测定血清 CC16 水平。作为一项体外研究，评估了屋尘螨变应原 1（Der p1）对气道上皮细胞（AECs）中 CC16 产生的时间依赖性影响；测试了 CC16 蛋白对氧化应激系统、气道炎症和重塑的影响。
哮喘患者的血清 CC16 水平明显高于 HCs（p<0.001），且与 FEV%呈正相关（r=0.352，p=0.005）。有 BDR 组的血清 CC16、FEV%和 MMEF%水平明显较低，但 FeNO 水平较高。血清 CC16 水平（<496.0ng/mL）可区分有 BDR 组和无 BDR 组（曲线下面积=0.74，p=0.004）。体外检测表明，Der p1 暴露可使 AEC 中 CC16 释放 1h，6h 后逐渐减少，随后 MMP-9 和 TIMP-1 产生。这些发现与氧化应激/抗氧化失衡有关，用 CC16 治疗（而非地塞米松）可恢复。
CC16 产生减少导致持续性气道炎症和肺功能下降。CC16 可能是 BDR 哮喘患者的潜在生物标志物。
