Alcohol Inhibits Organic Dust-Induced ICAM-1 Expression on Bronchial Epithelial Cells
AbstractAims: 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. Methods: 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 ad libitum ethanol (20%) in drinking water for 8 weeks followed by daily intranasal inhalation of HDE or saline during the final two weeks. Mice were sacrificed and lung sections immunostained for ICAM-1. Results: 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. Conclusions: 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. View Full-Text
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Wyatt, T.A.; Canady, K.; Heires, A.J.; Poole, J.A.; Bailey, K.L.; Nordgren, T.M.; Romberger, D.J. Alcohol Inhibits Organic Dust-Induced ICAM-1 Expression on Bronchial Epithelial Cells. Safety 2017, 3, 5.
Wyatt TA, Canady K, Heires AJ, Poole JA, Bailey KL, Nordgren TM, Romberger DJ. Alcohol Inhibits Organic Dust-Induced ICAM-1 Expression on Bronchial Epithelial Cells. Safety. 2017; 3(1):5.Chicago/Turabian Style
Wyatt, Todd A.; Canady, Kerry; Heires, Art J.; Poole, Jill A.; Bailey, Kristina L.; Nordgren, Tara M.; Romberger, Debra J. 2017. "Alcohol Inhibits Organic Dust-Induced ICAM-1 Expression on Bronchial Epithelial Cells." Safety 3, no. 1: 5.
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