Wyatt Todd A, Canady Kerry, Heires Art J, Poole Jill A, Bailey Kristina L, Nordgren Tara M, Romberger Debra J
Pulmonary, Critical Care, Sleep & Allergy Division of the Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198; USA.
Department of Environmental, Agricultural, & Occupational Health, University of Nebraska Medical Center, Omaha, NE, 68198-5910.
Safety (Basel). 2017 Mar;3(1). doi: 10.3390/safety3010005. Epub 2017 Jan 7.
Aims: Exposure to dusts/bioaerosols in concentrated animal feeding operations (CAFOs) results in inflammatory lung diseases in workers. Hog CAFOs dust extract (HDE) increases expression of intercellular adhesion molecule-1 (ICAM-1), neutrophil adhesion, and TNFα release in bronchial epithelial cells. Alcohol consumption is increasingly recognized to impair lung immunity. We hypothesized that alcohol impairs HDE-induced TNFα, ICAM-1 expression and neutrophil adhesion by directly inhibiting TNFα converting enzyme (TACE) activity.
Bronchial epithelial cells (BEAS-2B) and primary human bronchial epithelial cells were pretreated with ethanol (EtOH) or TACE inhibitor. ICAM-1 surface expression, TNFα release, and TACE activity were analyzed following HDE stimulation. The effect of alcohol and TACE inhibition on HDE-regulated epithelial cell/neutrophil adhesion interactions was investigated. Finally, utilizing an established animal model, C57BL/6 mice were fed ethanol (20%) in drinking water for 8 wk followed by daily intranasal inhalation of HDE or saline during the final two weeks. Mice were sacrificed and lung sections immunostained for ICAM-1.
Pretreatment with alcohol or TACE inhibitor significantly decreased HDE-induced ICAM-1 expression and TNFα release. HDE augmented neutrophil adhesion to epithelial cells, which was decreased with alcohol (32% decrease) or TACE inhibitor (55% decrease) pretreatment. TACE activity increased following HDE exposure, but TACE activity was inhibited following alcohol pretreatment. Alcohol-fed mice demonstrated decreased HDE-induced airway epithelium ICAM-1 expression.
Alcohol diminishes HDE-induced ICAM-1 expression, TNFα release, and neutrophil adhesion via inhibition of TACE activity. These results suggest that alcohol may be an important modulator of lung innate immune responses following CAFO exposure.
目的：在集约化动物饲养场（CAFOs）中接触粉尘/生物气溶胶会导致工人患炎性肺病。猪CAFOs粉尘提取物（HDE）可增加支气管上皮细胞中细胞间黏附分子-1（ICAM-1）的表达、中性粒细胞黏附及肿瘤坏死因子α（TNFα）释放。饮酒对肺免疫的损害作用日益受到认可。我们假设酒精通过直接抑制TNFα转换酶（TACE）活性来损害HDE诱导的TNFα、ICAM-1表达及中性粒细胞黏附。
用乙醇（EtOH）或TACE抑制剂预处理支气管上皮细胞（BEAS-2B）和原代人支气管上皮细胞。在HDE刺激后分析ICAM-1表面表达、TNFα释放及TACE活性。研究酒精和TACE抑制对HDE调节的上皮细胞/中性粒细胞黏附相互作用的影响。最后，利用已建立的动物模型，给C57BL/6小鼠饮用含20%乙醇的水8周，然后在最后两周每天经鼻吸入HDE或生理盐水。处死小鼠，对肺切片进行ICAM-1免疫染色。
用酒精或TACE抑制剂预处理可显著降低HDE诱导的ICAM-1表达和TNFα释放。HDE增强了中性粒细胞与上皮细胞的黏附，而酒精（降低32%）或TACE抑制剂预处理（降低55%）可减少这种黏附。HDE暴露后TACE活性增加，但酒精预处理后TACE活性受到抑制。饮用酒精的小鼠HDE诱导的气道上皮ICAM-１表达降低。
酒精通过抑制TACE活性减少HDE诱导的ICAM-1表达、TNFα释放及中性粒细胞黏附。这些结果表明，酒精可能是CAFO暴露后肺固有免疫反应的重要调节因子。
