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Autoimmune Hepatitis Induced by Syngeneic Liver Cytosolic Proteins Biotransformed by Alcohol Metabolites THIELE ET AL. INDUCTION OF HEPATITIS USING ALCOHOL METABOLITES.
- Source :
- Alcoholism: Clinical & Experimental Research; Dec2010, Vol. 34 Issue 12, p2126-2136, 11p
- Publication Year :
- 2010
-
Abstract
- Aldehydes that are produced following the breakdown of ethanol (acetaldehyde) and lipid peroxidation of membranes (malondialdehyde) have been shown to bind (adduct) proteins. Additionally, these two aldehydes can combine (MAA) on nonsyngeneic and syngeneic proteins to initiate numerous immune responses to the unmodified part of the protein in the absence of an adjuvant. Therefore, these studies provide a potential mechanism for the development of antigen-specific immune responses resulting in liver damage should syngeneic liver proteins be adducted with MAA. This study sought to test whether MAA-modified syngeneic liver cytosolic proteins administered daily in the absence of adjuvant into C57BL/6 mice abrogates tolerance to initiate a MAA-induced autoimmune-like hepatitis. In mice immunized with MAA-modified cytosols, there was an increase in liver damage as assessed by aspartate aminotransferase/alanine aminotransferase levels that correlated with liver pathology scores and the presence of the pro-fibrotic factors, smooth muscle actin, TGF-β, and collagen. IgG antibodies and T-cell proliferative responses specific for cytosolic proteins were also detected. Pro-inflammatory cytokines were produced in the livers of animals exposed to MAA-modified cytosols. Finally, transfer of immunized T cells to naïve animals caused biochemical and histological evidence of liver damage. These data demonstrate that a disease with an autoimmune-like pathophysiology can be generated in this animal model using soluble MAA-modified syngeneic liver cytosols as the immunogen. These studies provide insight into potential mechanism(s) that the metabolites of alcohol may play in contributing to the onset of an autoimmune-like disease in patients with alcoholic liver disease. [ABSTRACT FROM AUTHOR]
- Subjects :
- COMPLICATIONS of alcoholism
ALDEHYDES
ANALYSIS of variance
ANIMAL experimentation
ASPARTATE aminotransferase
AUTOIMMUNE diseases
COMPUTER software
STATISTICAL correlation
ENZYME-linked immunosorbent assay
ETHANOL
HEPATITIS
HISTOLOGICAL techniques
IMMUNOGLOBULINS
MICE
PROTEINS
RESEARCH funding
T cells
WESTERN immunoblotting
DATA analysis
ALANINE aminotransferase
Subjects
Details
- Language :
- English
- Volume :
- 34
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Alcoholism: Clinical & Experimental Research
- Publication Type :
- Academic Journal
- Accession number :
- 55255001
- Full Text :
- https://doi.org/10.1111/j.1530-0277.2010.01309.x