Premium
Effect of trichloroethylene exposure on autoimmune‐mediated cholangitis in NOD.c3c4 mice
Author(s) -
Sullivan Bradley P.,
Kassel Karen M.,
Luyendyk James P.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.134.2
Subject(s) - nod , autoimmunity , nod mice , fibrosis , cirrhosis , autoimmune disease , primary biliary cirrhosis , liver disease , immunology , trichloroethylene , medicine , immune system , endocrinology , chemistry , antibody , diabetes mellitus , environmental chemistry
Primary biliary cirrhosis (PBC) is characterized by autoimmune‐mediated destruction of bile ducts and has both genetic and environmental components. Specific chemicals that cause PBC have not been identified. Previous studies have shown that trichloroethylene (TCE) exposure promotes autoimmunity. We evaluated the capacity of TCE exposure to enhance liver disease in a mouse model of cholangitis. NOD.c3c4 mice spontaneously develop autoimmune‐mediated liver disease with features resembling PBC including portal inflammation and fibrosis. Nine week old NOD.c3c4 mice were exposed to TCE (0.5 mg/ml) or its vehicle (1% Cremaphor‐EL) via drinking water for 4 weeks. TCE exposure increased serum alanine aminotransferase (ALT) activity and serum bile acid levels in NOD.c3c4 mice, but did not affect biliary cyst area, another feature of liver disease in these mice. Interestingly, TCE exposure suppressed mRNA levels of early growth response 1 (Egr‐1), a transcription factor shown to limit fibrosis. Of importance, TCE exposure increased hepatic collagen expression in NOD.c3c4 mice. In contrast, NOD.ShiLtj mice exposed to TCE did not develop liver disease or fibrosis. These results suggest that TCE exposure enhances liver disease in NOD.c3c4 mice, and further highlights the possibility of utilizing these mice to study gene‐environment interactions critical for development of autoimmune‐mediated liver disease.