Department of Internal Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, University of Nebraska Medical Center, 985910 Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Internal Medicine, Division of Allergy & Immunology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Biomolecules. 2024 Jul 12;14(7):843. doi: 10.3390/biom14070843.
Agricultural workers exposed to organic dust from swine concentrated animal feeding operations (CAFOs) have increased chances of contracting chronic lung disease. Mucociliary clearance represents a first line of defense against inhaled dusts, but organic dust extracts (ODEs) from swine barns cause cilia slowing, leading to decreased bacterial clearance and increased lung inflammation. Because nutritional zinc deficiency is associated with chronic lung disease, we examined the role of zinc supplementation in ODE-mediated cilia slowing. Ciliated mouse tracheal epithelial cells were pretreated with 0-10 µg/mL ZinPro for 1 h, followed by treatment with 5% ODE for 24 h. Cilia beat frequency (CBF) and protein kinase C epsilon (PKCε) activity were assayed. ODE treatment resulted in cilia slowing after 24 h, which was reversed with 0.5 and 1.0 µg/mL ZinPro pre-treatment. No zinc protection was observed at 50 ng/mL, and ciliated cells detached at high concentrations (100 µg/mL). ZinPro alone produced no changes in the baseline CBF and showed no toxicity to the cells at concentrations of up to 10 µg/mL. Pre-treatment with ZinPro inhibited ODE-stimulated PKCε activation in a dose-dependent manner. Based on ZinPro's superior cell permeability compared to zinc salts, it may be therapeutically more effective at reversing ODE-mediated cilia slowing through a PKCε pathway. These data demonstrate that zinc supplementation may support the mucociliary transport apparatus in the protection of CAFO workers against dust-mediated chronic lung disease.
接触来自集约化养猪场（CAFO）的有机粉尘的农业工人患慢性肺病的几率增加。黏液纤毛清除代表了抵御吸入粉尘的第一道防线，但来自猪舍的有机粉尘提取物（ODE）会导致纤毛运动减缓，从而导致细菌清除减少和肺部炎症增加。由于营养性锌缺乏与慢性肺病有关，我们研究了锌补充剂在 ODE 介导的纤毛运动减缓中的作用。用 0-10 µg/mL 的 ZinPro 预处理有纤毛的小鼠气管上皮细胞 1 h，然后用 5% ODE 处理 24 h。测定纤毛摆动频率（CBF）和蛋白激酶 C ɛ（PKCε）活性。ODE 处理 24 h 后导致纤毛运动减缓，用 0.5 和 1.0 µg/mL 的 ZinPro 预处理可逆转这种减缓。用 50 ng/mL 的 ZinPro 则观察不到锌的保护作用，而高浓度（100 µg/mL）则会使纤毛细胞脱落。ZinPro 单独使用不会改变基线 CBF，并且在高达 10 µg/mL 的浓度下对细胞没有毒性。ZinPro 预处理以剂量依赖性方式抑制 ODE 刺激的 PKCε 激活。基于 ZinPro 比锌盐具有更好的细胞通透性，它可能通过 PKCε 途径在逆转 ODE 介导的纤毛运动减缓方面更具治疗效果。这些数据表明，锌补充剂可能通过支持黏液纤毛转运装置来保护 CAFO 工人免受粉尘介导的慢性肺病。
