Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

Abstract

Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs) are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF), tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon) activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability of the lung to activate PKCε-dependent inflammatory pathways to environmental dust exposure. These data also define alcohol as an important co-exposure agent to consider in the study of inhalation injury responses.

Alcohol Decreases Organic Dust‐Stimulated Airway Epithelial TNF‐Alpha Through a Nitric Oxide and Protein Kinase‐Mediated Inhibition of TACE

“…In our study, we observed pro-inflammatory cytokines that are responsible for neutrophil and lymphocyte recruitment increase with a 5% HDE exposure in the BEAS-2B cell line. We also observed a blunting effect in the airway cells that were exposed to HDE and EtOH, which would be in accordance with our in vivo model histological findings (McCaskill et al, 2012). A decrease in pro-inflammatory cytokines (TNFα, IL-6, IL-8) as seen in Figures 1, 5 and 6 corroborates the published observations of decreased lung lavage lymphocytes and mononuclear cell aggregates in alcohol-fed mice challenged with HDE.…”

“…In studies conducted with a mouse model, mice that consumed ad libitum EtOH for 6 wk and inhaled HDE for 3 wk had fewer neutrophils and lymphocytes present in bronchoalveolar lavage fluid (BALF) compared to mice that were only exposed to HDE (McCaskill et al, 2012). In our study, we observed pro-inflammatory cytokines that are responsible for neutrophil and lymphocyte recruitment increase with a 5% HDE exposure in the BEAS-2B cell line.…”

“…Alcohol exposure, however, negatively affects the normal inflammatory response to hog barn dusts in mice. Elevations in lung lavage inflammatory cytokines and mononuclear cell aggregates normally observed in histological evaluations as a result of repetitive hog barn dust extract exposure (HDE) are abrogated in mice that were previously fed alcohol (McCaskill et al, 2012). Mice treated with the concurrent exposure of alcohol and HDE had a decrease in weight and experienced 20% mortality.…”

cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells

“…Precision-cut lung (PCL) slices were made as previously described (14). Briefly, C57BL/6 mice were killed, and the lungs were inflated with low-melting-point agarose (Invitrogen, Carlsbad, CA).…”

Chronic ethanol exposure alters the lung proteome and leads to mitochondrial dysfunction in alveolar type 2 cells

“…All animals were given standard chow ad libitum; dietary intake was comparable in both groups. With these general approaches, the blood alcohol levels of animals following chronic ethanol consumption has been reported to be 0.08% (38,54).…”