PU.1 and Nrf2 signaling in vivo in our Klebsiella pneumonia model. Therefore, we can only speculate that restoration of PU.1 and Nrf2 signaling through zinc supplementation is mechanistic in improving bacterial clearance. Additionally, we did not detect any zinc-dependent interactions between PU.1 and Nrf2 by the supershift assay in alveolar macrophages from control-fed rats. Perhaps these pathways become interdependent (and this interdependence is zinc-dependent) in response to acute or chronic stresses such as alcohol abuse. Whether or not these two pathways are interdependent or simply are activated in parallel, they are clearly critical for defense against inflammatory stresses and evidence is emerging from these experimental studies that alcohol interferes with both pathways by decreasing zinc bioavailability within the alveolar space.
