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Gold- and silver-induced murine autoimmunity - requirement for cytokines and CD28 in murine heavy metal-induced autoimmunity
Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
Scripps Research Institute.
Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
2009 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 155, no 3, 567-576 p.Article in journal (Refereed) Published
Abstract [en]

Treatment with gold in the form of aurothiomaleate, silver or mercury (Hg) in genetically susceptible mouse strains (H-2(s) ) induces a systemic autoimmune condition characterized by anti-nuclear antibodies targeting the 34-kDa nucleolar protein fibrillarin, as well as lymphoproliferation and systemic immune-complex (IC) deposits. In this study we have examined the effect of single-gene deletions for interferon (IFN)-gamma, interleukin (IL)-4, IL-6 or CD28 in B10.S (H-2(s) ) mice on heavy metal-induced autoimmunity. Targeting of the genes for IFN-gamma, IL-6 or CD28 abrogated the development of both anti-fibrillarin antibodies (AFA) and IC deposits using a modest dose of Hg (130 mu g Hg/kg body weight/day). Deletion of IL-4 severely reduced the IgG1 AFA induced by all three metals, left the total IgG AFA response intact, but abrogated the Hg-induced systemic IC deposits. In conclusion, intact IFN-gamma and CD28 genes are necessary for induction of AFA with all three metals and systemic IC deposits using Hg, while lack of IL-4 distinctly skews the metal-induced AFA response towards T helper type 1. In a previous study using a higher dose of Hg (415 mu g Hg/kg body weight/day), IC deposits were preserved in IL-4(-/-) and IL-6(-/-) mice, and also AFA in the latter mice. Therefore, the attenuated autoimmunity following loss of IL-4 and IL-6 is dose-dependent, as higher doses of Hg are able to override the attenuation observed using lower doses.

Place, publisher, year, edition, pages
2009. Vol. 155, no 3, 567-576 p.
Keyword [en]
autoimmunity, CD28, cytokines, gold, silver
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-16880DOI: 10.1111/j.1365-2249.2008.03831.xOAI: oai:DiVA.org:liu-16880DiVA: diva2:174427
Available from: 2009-02-22 Created: 2009-02-20 Last updated: 2017-12-13

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Havarinasab, SaidHultman, Per

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Molecular and Immunological Pathology Faculty of Health SciencesDepartment of Clinical Pathology and Clinical Genetics
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