Background
Previous studies have shown that chronic ethanol (EtOH) ingestion
Conclusions
EtOH treatment increased oxidant stress, TGF-β(1) production, and alternative activation in NR8383 cells. However, GSH supplementation and ablation of TGF-β(1) signaling prevented these effects. This suggested that the EtOH-induced switch to an M2 phenotype was a result of decreased antioxidant availability and increased TGF-β(1) signaling. Preventing EtOH-induced induction of alternative activation may improve alveolar macrophage function in alcoholic subjects and decrease the risk of respiratory infections.
Methods
Primary rat alveolar macrophages and the alveolar macrophages cell line NR8383 were treated with 0.08% EtOH ± the antioxidant glutathione (GSH) or a TGF-β(1) neutralizing antibody for 5 days. Outcome measures included TGF-β(1) production, reactive oxygen species (ROS) production, phagocytic capacity, and expression of markers of M2 activation.
Results
Chronic EtOH treatment greatly decreased alveolar macrophage phagocytic function, increased ROS production, increased TGF-β(1) , and increased expression of markers of M2 activation. GSH supplementation and inhibition of TGF-β(1) signaling during EtOH treatment prevented these alterations. Conclusions: EtOH treatment increased oxidant stress, TGF-β(1) production, and alternative activation in NR8383 cells. However, GSH supplementation and ablation of TGF-β(1) signaling prevented these effects. This suggested that the EtOH-induced switch to an M2 phenotype was a result of decreased antioxidant availability and increased TGF-β(1) signaling. Preventing EtOH-induced induction of alternative activation may improve alveolar macrophage function in alcoholic subjects and decrease the risk of respiratory infections.