ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Cathepsin B regulates the appearance and severity of mercury-induced inflammation and autoimmunity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Susceptibility to systemic autoimmunity rather than the presence of the HLA-DR4 peptide binding domain alone leads to severe inflammatory arthritis following inhalation of crystalline silica.Particle and fibre toxicology · 2026Article
- Crystalline silica exposure induces multiple systemic autoimmune phenotypes including inflammatory arthritis and nephritis in Collaborative Cross mice with differing sub-clinical autoimmune profiles.bioRxiv : the preprint server for biology · 2025Article
- Drug-Induced Membranous Nephropathy: Piecing Together Clues to Understand Disease Mechanisms.Journal of the American Society of Nephrology : JASN · 2025Review
- Associations of metal mixtures with metabolic-associated fatty liver disease and non-alcoholic fatty liver disease: NHANES 2003-2018.Frontiers in public health · 2023Article
- Peritonitis Due to Appendicitis Related to Mercury Sequestration: An Unusual Peruvian Case Report.Cureus · 2022Article
- Molecular Features of CA-074 pH-Dependent Inhibition of Cathepsin B.Biochemistry · 2022Article
- The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy.Frontiers in pharmacology · 2022Review
- Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration.Frontiers in neuroscience · 2022Review
- In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.Hepatology (Baltimore, Md.) · 2021Article
- KIF5A-dependent axonal transport deficiency disrupts autophagic flux in trimethyltin chloride-induced neurotoxicity.Autophagy · 2021Article
- Mechanisms of Environment-Induced Autoimmunity.Annual review of pharmacology and toxicology · 2021Article
- Association of Fish Consumption and Mercury Exposure During Pregnancy With Metabolic Health and Inflammatory Biomarkers in Children.JAMA network open · 2020Article
- Mercury-induced inflammation and autoimmunity.Biochimica et biophysica acta. General subjects · 2019Review
- Cathepsin B inhibition ameliorates leukocyte-endothelial adhesion in the BTBR mouse model of autism.CNS neuroscience & therapeutics · 2019Article
- Development of a Gill Assay Library for Ecological Proteomics of Threespine Sticklebacks (Molecular & cellular proteomics : MCP · 2018Article
- Environmental Xenobiotic Exposure and Autoimmunity.Current opinion in toxicology · 2018Article
- Silicosis and Silica-Induced Autoimmunity in the Diversity Outbred Mouse.Frontiers in immunology · 2018Article
- Article
- Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- From the Cover: Interplay Between IFN-γ and IL-6 Impacts the Inflammatory Response and Expression of Interferon-Regulated Genes in Environmental-Induced Autoimmunity.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Susceptibility and resistance to systemic autoimmunity are genetically regulated. This is particularly true for murine mercury-induced autoimmunity (mHgIA) where DBA/2J mice are considered resistant to disease including polyclonal B cell activation, autoantibody responses, and immune complex deposits. To identify possible mechanisms for the resistance to mHgIA, we exposed mHgIA sensitive B10.S and resistant DBA/2J mice to HgCl2 and assessed inflammation and pro-inflammatory responses at the site of exposure and subsequent development of markers of systemic autoimmunity. DBA/2J mice showed little evidence of induration at the site of exposure, expression of proinflammatory cytokines, T cell activation, or autoantibody production, although they did exhibit increased levels of total serum IgG and IgG1. In contrast B10.S mice developed significant inflammation together with increased expression of inflammasome component NLRP3, proinflammatory cytokines IL-1β, TNF-α, and IFN-γ, hypergammaglobulinemia, splenomegaly, CD4(+) T-cell activation, and production of autoantibodies. Inflammation in B10.S mice was associated with a selective increase in activity of cysteine cathepsin B but not cathepsins L or S. Increased cathepsin B activity was not dependent on cytokines required for mHgIA but treatment with CA-074, a cathepsin B inhibitor, led to transient reduction of local induration, expression of inflammatory cytokines, and subsequent attenuation of the systemic adaptive immune response. These findings demonstrate that sensitivity to mHgIA is linked to an early cathepsin B regulated inflammatory response which can be pharmacologically exploited to abrogate the subsequent adaptive autoimmune response which leads to disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.