Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis

Jessica L. Ray, Anna K. Kopec, Nikita Joshi, Holly Cline-Fedewa, Lawrence H. Lash, Kurt J. Williams, Patrick S Leung, M. Eric Gershwin, James P. Luyendyk

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL+/+mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model.

Original languageEnglish (US)
Article numberkfw264
Pages (from-to)428-437
Number of pages10
JournalToxicological Sciences
Volume156
Issue number2
DOIs
StatePublished - Apr 1 2017

Fingerprint

Trichloroethylene
Cholangitis
Liver
Wounds and Injuries
Autoimmunity
Inflammation
Autoimmune Diseases
B-Lymphocytes
Autoimmune Hepatitis
T-cells
Gene expression
Drinking Water
Interleukin-10
transforming growth factor-beta type II receptor
Liver Diseases
Anti-Idiotypic Antibodies
Hepatocytes
Anti-Inflammatory Agents
Theoretical Models
Necrosis

Keywords

  • Autoimmune
  • Cholangitis
  • Immunotoxicology
  • Liver
  • Primary biliary
  • Systems toxicology
  • Trichloroethylene

ASJC Scopus subject areas

  • Toxicology

Cite this

Ray, J. L., Kopec, A. K., Joshi, N., Cline-Fedewa, H., Lash, L. H., Williams, K. J., ... Luyendyk, J. P. (2017). Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis. Toxicological Sciences, 156(2), 428-437. [kfw264]. https://doi.org/10.1093/toxsci/kfw264

Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis. / Ray, Jessica L.; Kopec, Anna K.; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H.; Williams, Kurt J.; Leung, Patrick S; Gershwin, M. Eric; Luyendyk, James P.

In: Toxicological Sciences, Vol. 156, No. 2, kfw264, 01.04.2017, p. 428-437.

Research output: Contribution to journalArticle

Ray, JL, Kopec, AK, Joshi, N, Cline-Fedewa, H, Lash, LH, Williams, KJ, Leung, PS, Gershwin, ME & Luyendyk, JP 2017, 'Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis', Toxicological Sciences, vol. 156, no. 2, kfw264, pp. 428-437. https://doi.org/10.1093/toxsci/kfw264
Ray JL, Kopec AK, Joshi N, Cline-Fedewa H, Lash LH, Williams KJ et al. Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis. Toxicological Sciences. 2017 Apr 1;156(2):428-437. kfw264. https://doi.org/10.1093/toxsci/kfw264
Ray, Jessica L. ; Kopec, Anna K. ; Joshi, Nikita ; Cline-Fedewa, Holly ; Lash, Lawrence H. ; Williams, Kurt J. ; Leung, Patrick S ; Gershwin, M. Eric ; Luyendyk, James P. / Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis. In: Toxicological Sciences. 2017 ; Vol. 156, No. 2. pp. 428-437.
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