title: Response of Differentiated Human Airway Epithelia to Alcohol Exposure andKlebsiella PneumoniaeChallenge.
abstract: Alcohol abuse has been associated with increased susceptibility to pulmonary infection. It is not fully defined how alcohol contributes to the host defense compromise. Here primary human airway epithelial cells were cultured at an air-liquid interface to form a differentiated and polarized epithelium. This unique culture model allowed us to closely mimic lung infection in the context of alcohol abuse by basolateral alcohol exposure and apical live bacterial challenge. Application of clinically relevant concentrations of alcohol for 24 hours did not significantly alter epithelial integrity or barrier function. When apically challenged with viableKlebsiella pneumoniae, the cultured epithelia had an enhanced tightness which was unaffected by alcohol. Further, alcohol enhanced apical bacterial growth, but not bacterial binding to the cells. The cultured epithelium in the absence of any treatment or stimulation had a base-level IL-6 and IL-8 secretion. Apical bacterial challenge significantly elevated the basolateral secretion of inflammatory cytokines including IL-2, IL-4, IL-6, IL-8, IFN-γ, GM-CSF, and TNF-α. However, alcohol suppressed the observed cytokine burst in response to infection. Addition of adenosine receptor agonists negated the suppression of IL-6 and TNF-α. Thus, acute alcohol alters the epithelial cytokine response to infection, which can be partially mitigated by adenosine receptor agonists.
authors.affiliation: Comprehensive Alcohol Research Center, Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Sammeta V
authors.initials: SV
authors.lastname: Raju
authors.affiliation: Comprehensive Alcohol Research Center, Department of Microbiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Painter
authors.affiliation: Comprehensive Alcohol Research Center, Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
authors.affiliation: Comprehensive Alcohol Research Center, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Comprehensive Alcohol Research Center, Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA ; Comprehensive Alcohol Research Center, Department of Microbiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA ; Comprehensive Alcohol Research Center, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Guoshun
authors.initials: G
authors.lastname: Wang
keywords: Adenosine receptor; Air-liquid interface culture; Alcohol; Cytokines; Epithelial barrier function; Human airway epithelia; Klebsiella pneumoniae bacteria