Trichloroethylene accelerates an autoimmune response by Th1 T cell activation in MRL +/+ mice
| Autor: | Kathleen M. Gilbert, Neil R. Pumford, Stephanie K. Jackson, Sarah J. Blossom, Joseph M. Griffin |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Mice Inbred MRL lpr Trichloroethylene medicine.medical_treatment T cell Blotting Western medicine.disease_cause Lymphocyte Activation Autoimmunity chemistry.chemical_compound Mice Immune system Internal medicine medicine Animals Interferon gamma Biotransformation Autoantibodies Pharmacology biology Th1 Cells Acquired immune system Cytokine medicine.anatomical_structure Endocrinology chemistry Immunoglobulin M Immunoglobulin G biology.protein Environmental Pollutants Female Antibody medicine.drug |
| Zdroj: | Immunopharmacology. 46(2) |
| ISSN: | 0162-3109 |
| Popis: | Trichloroethylene (1,1,2-trichloroethene) is a major environmental contaminant. There is increasing evidence relating exposure to trichloroethylene with autoimmunity. To investigate potential mechanisms, we treated the autoimmune-prone MRL +/+ mice with trichloroethylene in the drinking water at 0, 2.5 or 5.0 mg/ml and sacrificed them at 4, 8 and 22 weeks. As early as 4 weeks of treatment, Western blot analysis showed a dose-dependent increase in the level of trichloroethylene-modified proteins, indicating that a reactive metabolite of trichloroethylene was formed. Significant increases in antinuclear antibodies (ANA) and total serum immunoglobulins were found following 4-8 weeks of trichloroethylene treatment, indicating that trichloroethylene was accelerating an autoimmune response. Investigation into possible mechanisms of this autoimmune response revealed that trichloroethylene treatment dramatically increased the expression of the activation marker CD44 on splenic CD4+ T cells at 4 weeks. In addition, splenic T cells from mice treated for 4 weeks with trichloroethylene secreted more IFN-gamma and less IL-4 than control T cells, consistent of a T-helper type 1 (Th1) type immune or inflammatory response. A specific immune response directed against dichloroacetylated proteins was found at 22 weeks of trichloroethylene treatment. Taken collectively, the results suggest that trichloroethylene treatment accelerated an autoimmune response characteristic of MRL +/+ mice in association with nonspecific activation of Th1 cells. In addition, long-term treatment with trichloroethylene led to the initiation of a trichloroethylene-specific immune response. |
| Databáze: | OpenAIRE |
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