{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang H"],"funding":["National Institute of Environmental Health Sciences","NIEHS NIH HHS","National Institutes of Health"],"pagination":["153468"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9998359"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["487"],"pubmed_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."],"journal":["Toxicology"],"pubmed_title":["Autophagy dysregulation in trichloroethene-mediated inflammation and autoimmune response."],"pmcid":["PMC9998359"],"funding_grant_id":["R01 ES026887","ES016302","R01 ES016302","ES026887","P30 ES030285"],"pubmed_authors":["Firoze Khan M","Wang G","Wang H","Banerjee N"],"additional_accession":[]},"is_claimable":false,"name":"Autophagy dysregulation in trichloroethene-mediated inflammation and autoimmune response.","description":"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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2025-04-22T15:03:04.888Z","creation":"2025-04-06T01:17:31.308Z"},"accession":"S-EPMC9998359","cross_references":{"pubmed":["36849104"],"doi":["10.1016/j.tox.2023.153468"]}}