| Low-dose inorganic mercury increases severity and frequency of chronic coxsackievirus-induced autoimmune myocarditis in mice. | |
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MedLine Citation:
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PMID: 21984480 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mercury is a widespread environmental contaminant with neurotoxic impacts that have been observed over a range of exposures. In addition, there is increasing evidence that inorganic mercury (iHg) and organic mercury (including methyl mercury) have a range of immunotoxic effects, including immune suppression and induction of autoimmunity. In this study, we investigated the effect of iHg on a model of autoimmune heart disease in mice induced by infection with coxsackievirus B3 (CVB3). We examined the role of timing of iHg exposure on disease; in some experiments, mice were pretreated with iHg (200 μg/kg, every other day for 15 days) before disease induction with virus inoculation, and in others, they were treated with iHg after the acute (viral) phase of disease but before the development of dilated cardiomyopathy (DCM). iHg alone had no effect on heart pathology. Pretreatment with iHg before CVB3 infection significantly increased the severity of chronic myocarditis and DCM compared with control animals receiving vehicle alone. In contrast, treatment with iHg after acute myocarditis did not affect the severity of chronic disease. The increased chronic myocarditis, fibrosis, and DCM induced by iHg pretreatment were not due to increased viral replication in the heart, which was unaltered by iHg treatment. iHg pretreatment induced a macrophage infiltrate and mixed cytokine response in the heart during acute myocarditis, including significantly increased interleukin (IL)-12, IL-17, interferon-γ, and tumor necrosis factor-α levels. IL-17 levels were also significantly increased in the spleen during chronic disease. Thus, we show for the first time that low-dose Hg exposure increases chronic myocarditis and DCM in a murine model. |
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Authors:
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Jennifer F Nyland; DeLisa Fairweather; Devon L Shirley; Sarah E Davis; Noel R Rose; Ellen K Silbergeld |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-10-09 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 125 ISSN: 1096-0929 ISO Abbreviation: Toxicol. Sci. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-22 Completed Date: 2012-06-06 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 134-43 Citation Subset: IM |
Affiliation:
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Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA. jnyland@uscmed.sc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Animals Autoimmune Diseases / chemically induced*, immunology, pathology, virology Cardiomyopathy, Dilated / chemically induced, immunology, pathology, virology Chronic Disease Coxsackievirus Infections / chemically induced*, immunology, pathology, virology Cytokines / immunology Disease Models, Animal Dose-Response Relationship, Drug Enterovirus B, Human / growth & development* Environmental Pollutants / toxicity* Heart / drug effects, virology Male Mercury Compounds / toxicity* Mice Mice, Inbred BALB C Myocarditis / chemically induced*, immunology, pathology, virology Myocardium / immunology, pathology Severity of Illness Index Spleen / immunology, pathology Virus Replication / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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K99/R00 ES015426/ES/NIEHS NIH HHS; T32 ES007141/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Environmental Pollutants; 0/Mercury Compounds |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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