Date on Master's Thesis/Doctoral Dissertation

8-2015

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Arteel, Gavin

Committee Co-Chair (if applicable)

Roman, Jesse

Committee Member

Roman, Jesse

Committee Member

Siskind, Leah

Committee Member

Hoyle, Gary

Committee Member

States, J. Christopher

Subject

Alcohol--Physiological effect; Alcohol--Pathophysiology; Lungs--Diseases

Abstract

The goal of this project is to characterize a new mouse model of alcohol-enhanced acute lung injury (ALI) and to determine the role of plasminogen activator inhibitor-1 (PAI-1) in this model. Male mice (WT and PAI-1-/-) were exposed to ethanol-containing Lieber-DeCarli diet or pair-fed control diet for 6 weeks; some animals were administered intraperitoneal lipopolysaccharide (LPS) prior to sacrifice. Chronic alcohol feeding enhanced induction of the chemokines MIP-2 and KC (murine IL-8 homologues) after LPS injection in wild type animals. This enhanced chemokine expression did not correlate with enhanced pulmonary neutrophil infiltration, however animals exposed to chronic ethanol showed sustained alveolar septal thickening and enhanced 4-HNE staining, indicative of inflammatory damage. Septal thickening was completely attenuated in PAI-1-/- animals. This work has developed a new mouse model which can be used to elucidate the mechanisms of alcohol-enhanced ALI. A potential role of PAI-1 in alcohol-enhanced ALI has also been identified.

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