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Med. Sci. 2013, 1(1), 2-19; doi:10.3390/medsci1010002
Article

Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge

1,†
, 2,‡
, 3,4
, 2,3,4
 and 1,2,4,*
1 Department of Genetics, Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA 2 Department of Microbiology, Immunology and Parasitology, Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA 3 Department of Physiology, Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA 4 Department of Medicine, Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA Present address: Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA. Present address: Division of Basic Pharmaceutical Sciences, School of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA.
* Author to whom correspondence should be addressed.
Received: 3 July 2013 / Revised: 19 July 2013 / Accepted: 22 July 2013 / Published: 26 July 2013
(This article belongs to the Special Issue Feature Papers 2013)
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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 h did not significantly alter epithelial integrity or barrier function. When apically challenged with viable Klebsiella 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.
Keywords: alcohol; human airway epithelia; air-liquid interface culture; Klebsiella pneumoniae bacteria; epithelial barrier function; cytokines; adenosine receptor alcohol; human airway epithelia; air-liquid interface culture; Klebsiella pneumoniae bacteria; epithelial barrier function; cytokines; adenosine receptor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Raju, S.V.; Painter, R.G.; Bagby, G.J.; Nelson, S.; Wang, G. Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge. Med. Sci. 2013, 1, 2-19.

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