title: Potential Role of the Gut/Liver/Lung Axis in Alcohol-Induced Tissue Pathology.
abstract: Both Alcoholic Liver Disease (ALD) and alcohol-related susceptibility to acute lung injury are estimated to account for the highest morbidity and mortality related to chronic alcohol abuse and, thus, represent a focus of intense investigation. In general, alcohol-induced derangements to both organs are considered to be independent and are often evaluated separately. However, the liver and lung share many general responses to damage, and specific responses to alcohol exposure. For example, both organs possess resident macrophages that play key roles in mediating the immune/inflammatory response. Additionally, alcohol-induced damage to both organs appears to involve oxidative stress that favors tissue injury. Another mechanism that appears to be shared between the organs is that inflammatory injury to both organs is enhanced by alcohol exposure. Lastly, altered extracellular matrix (ECM) deposition appears to be a key step in disease progression in both organs. Indeed, recent studies suggest that early subtle changes in the ECM may predispose the target organ to an inflammatory insult. The purpose of this chapter is to review the parallel mechanisms of liver and lung injury in response to alcohol consumption. This chapter will also explore the potential that these mechanisms are interdependent, as part of a gut-liver-lung axis.
authors.affiliation: Departments of Pharmacology and Toxicology and the University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292, USA. veronica_massey@med.unc.edu.
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Massey
authors.affiliation: Departments of Pharmacology and Toxicology and the University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292, USA. juliane.beier@louisville.edu.
authors.forename: Juliane I
authors.initials: JI
authors.lastname: Beier
authors.affiliation: Department of Medicine University of Louisville Health Sciences Center, Louisville, KY 40292, USA. j.ritzenthaler@louisville.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ritzenthaler
authors.affiliation: Departments of Pharmacology and Toxicology and the University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292, USA. j0roma02@exchange.louisville.edu.|Department of Medicine University of Louisville Health Sciences Center, Louisville, KY 40292, USA. j0roma02@exchange.louisville.edu.
authors.forename: Jesse
authors.initials: J
authors.lastname: Roman
authors.affiliation: Departments of Pharmacology and Toxicology and the University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292, USA. gavin.arteel@louisville.edu.
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Arteel
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D000431:Ethanol / Q000633:toxicity; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D000431:Ethanol
keywords: ethanol; extracellular matrix; hepatic; inflammation; pulmonary