The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yin, M.
Right arrow Articles by Thurman, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yin, M.
Right arrow Articles by Thurman, R. G.
The Journal of Immunology, 2001, 166: 4737-4742.
Copyright © 2001 by The American Association of Immunologists

Reduced Early Alcohol-Induced Liver Injury in CD14-Deficient Mice1

Ming Yin*, Blair U. Bradford2,*, Michael D. Wheeler*, Takehiko Uesugi*, Matthias Froh*, Sanna M. Goyert{dagger} and Ronald G. Thurman*

* Department of Pharmacology, Laboratory of Hepatobiology and Toxicology, University of North Carolina, Chapel Hill, NC 27599; and {dagger} Division of Molecular Medicine, North Shore University Hospital, Cornell University Medical College, Manhasset, NY 11030

Activation of Kupffer cells by gut-derived endotoxin is associated with alcohol-induced liver injury. Recently, it was shown that CD14-deficient mice are more resistant to endotoxin-induced shock than wild-type controls. Therefore, this study was designed to investigate the role of CD14 receptors in early alcohol-induced liver injury using CD14 knockout and wild-type BALB/c mice in a model of enteral ethanol delivery. Animals were given a high-fat liquid diet continuously with ethanol or isocaloric maltose-dextrin as control for 4 wk. The liver to body weight ratio in wild-type mice (5.8 ± 0.3%) was increased significantly by ethanol (7.3 ± 0.2%) but was not altered by ethanol in CD14-deficient mice. Ethanol elevated serum alanine aminotransferase levels nearly 3-fold in wild-type mice, but not in CD14-deficient mice. Wild-type and knockout mice given the control high-fat diet had normal liver histology, whereas ethanol caused severe liver injury (steatosis, inflammation, and necrosis; pathology score = 3.8 ± 0.4). In contrast, CD14-deficient mice given ethanol showed minimal hepatic changes (score = 1.6 ± 0.3, p < 0.05). Additionally, NF-{kappa}B, TGF-{beta}, and TNF-{alpha} were increased significantly in wild-type mice fed ethanol but not in the CD14 knockout. Thus, chronic ethanol feeding caused more severe liver injury in wild-type than CD14 knockouts, supporting the hypothesis that endotoxin acting via CD14 plays a major role in the development of early alcohol-induced liver injury.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Q. Cao, K. M. Mak, and C. S. Lieber
Cytochrome P4502E1 primes macrophages to increase TNF-{alpha} production in response to lipopolysaccharide
Am J Physiol Gastrointest Liver Physiol, July 1, 2005; 289(1): G95 - G107.
[Abstract] [Full Text] [PDF]

Home page
 Alcohol AlcoholHome page
J. Frank, K. Witte, W. Schrodl, and C. Schutt
CHRONIC ALCOHOLISM CAUSES DELETERIOUS CONDITIONING OF INNATE IMMUNITY
Alcohol Alcohol., September 1, 2004; 39(5): 386 - 392.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
L. E. Nagy
Recent Insights into the Role of the Innate Immune System in the Development of Alcoholic Liver Disease
Experimental Biology and Medicine, September 1, 2003; 228(8): 882 - 890.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Mullarkey, J. R. Rose, J. Bristol, T. Kawata, A. Kimura, S. Kobayashi, M. Przetak, J. Chow, F. Gusovsky, W. J. Christ, et al.
Inhibition of Endotoxin Response by E5564, a Novel Toll-Like Receptor 4-Directed Endotoxin Antagonist
J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1093 - 1102.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. D. Wheeler and R. G. Thurman
Up-regulation of CD14 in Liver Caused by Acute Ethanol Involves Oxidant-dependent AP-1 Pathway
J. Biol. Chem., February 28, 2003; 278(10): 8435 - 8441.
[Abstract] [Full Text] [PDF]

Home page
 Innate ImmunityHome page
E. Jirillo, D. Caccavo, T. Magrone, E. Piccigallo, L. Amati, A. Lembo, C. Kalis, and M. Gumenscheimer
Review: The role of the liver in the response to LPS: experimental and clinical findings
Innate Immunity, October 1, 2002; 8(5): 319 - 327.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
G. L. Su, S. M. Goyert, M.-H. Fan, A. Aminlari, K. Q. Gong, R. D. Klein, A. Myc, W. H. Alarcon, L. Steinstraesser, D. G. Remick, et al.
Activation of human and mouse Kupffer cells by lipopolysaccharide is mediated by CD14
Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G640 - G645.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
G. L. Su
Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation
Am J Physiol Gastrointest Liver Physiol, August 1, 2002; 283(2): G256 - G265.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Uesugi, M. Froh, G. E. Arteel, B. U. Bradford, M. D. Wheeler, E. Gabele, F. Isayama, and R. G. Thurman
Role of Lipopolysaccharide-Binding Protein in Early Alcohol-Induced Liver Injury in Mice
J. Immunol., March 15, 2002; 168(6): 2963 - 2969.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.