Autophagy dysregulation in trichloroethene-mediated inflammation and autoimmune response.

Abstract

Trichloroethene (TCE), an organic solvent extensively used for degreasing metals, can cause inflammatory autoimmune disorders [i.e., systemic lupus erythematosus (SLE) and autoimmune hepatitis] from both environmental and occupational exposure. Autophagy has emerged as a pivotal pathogenic factor in various autoimmune diseases. However, role of autophagy dysregulation in TCE-mediated autoimmunity is largely unknown. Here, we investigate whether autophagy dysregulation contributes to pathogenesis of TCE-mediated autoimmune responses. Using our established mouse model, we observed TCE-treated mice had elevated MDA-protein adducts, microtubule-associated protein light chain 3 conversion (LC3-II/LC3-I), beclin-1, phosphorylation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) phosphorylation in the livers of MRL+ /+ mice. Suppression of oxidative stress with antioxidant N-acetylcysteine (NAC) effectively blocked TCE-mediated induction of autophagy markers. On the other hand, pharmacological autophagy induction with rapamycin significantly reduced TCE-mediated hepatic inflammation (NLRP3, ASC, Caspase1 and IL1-β mRNA levels), systemic cytokines (IL-12 and IL-17) and autoimmune responses (ANA and anti-dsDNA levels). Taken together, these results suggest that autophagy plays a protective role against TCE-mediated hepatic inflammation and autoimmunity in MRL+ /+ mice. These novel findings on the regulation of autophagy could help in designing therapeutic strategies for chemical exposure-mediated autoimmune responses.

• Authors: Hui Wang, Nivedita Banerjee, Gangduo Wang, M Firoze Khan
• Journal: Toxicology (Toxicology) Vol. 487 Pg. 153468 (03 15 2023) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 36849104 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Solvents
• Trichloroethylene

Topics

• Animals
• Mice
• Autoimmune Diseases (chemically induced)
• Autoimmunity
• Autophagy
• Inflammation (chemically induced)
• Solvents (toxicity)
• Trichloroethylene (toxicity)