| Popis: |
Eugene Roscioli,1,2 Hubertus PA Jersmann,1,2 Susan Lester,2,3 Arash Badiei,1,2 Andrew Fon,1,2 Peter Zalewski,2,4 Sandra Hodge1,2 1Department of Thoracic Medicine, Royal Adelaide Hospital, 2Department of Medicine, The University of Adelaide, Adelaide, 3Department of Rheumatology, 4Cardiology Unit, The Queen Elizabeth Hospital, Woodville, SA, Australia Abstract: There is now convincing evidence that the airway epithelium drives the pathogenesis of COPD. A major aspect of this is the disease-related reduction in barrier function that is potentiated by dysregulation of tight junction (TJ) protein complexes. However, a significant number of studies using in vitro smoke exposure models have not observed alterations in barrier permeability. We have previously shown that zinc (Zn) is an influential cytoprotective factor for the airway epithelium, and its depletion by cigarette smoke produces disease-related modifications consistent with inflammatory changes in COPD. We hypothesized that Zn deficiency is a significant co-stimulus with cigarette smoke extract (CSE) for potentiating the leaky barrier phenotype exhibited in COPD. We employed an ex vivo model of differentiated human airway epithelium exposed to Zn depletion and CSE to determine the contribution of Zn in maintaining normal epithelial permeability. Western blot analysis demonstrated a significant downregulation of the TJ proteins such as ZO-1 (–1.93-fold, P |
