| Treatment with a toll-like receptor inhibitory GpG oligonucleotide delays and attenuates lupus nephritis in NZB/W mice. | |
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MedLine Citation:
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PMID: 19845477 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of the innate immune system by DNA containing hypomethylated CpG motifs has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we examined the consequences of immunostimulatory CpG-oligodeoxynucleotide (ODN) and inhibitory GpG-ODN treatment in the NZB x NZW F1 (NZB/W) murine model of SLE. Beginning at 5 months of age, we administered CpG-ODN or GpG-ODN at regular intervals to female NZB/W animals. We also determined the effects of ODN administration on NZB/W mouse lymphocyte function, and the specificity of ODN binding to Toll-like receptors (TLRs) other than TLR-9. While CpG-ODN treatment did not appear to have a major impact on disease severity, GpG-ODN treatment significantly delayed the onset of proteinuria in NZB/W mice. Interestingly, short-term GpG-ODN treatment promoted Th2-type T and B cell responses, and inhibited B lymphocyte proliferation in vitro. On the other hand, extended GpG-ODN treatment did not result in sustained Th2 responses or significantly reduced renal disease. Moreover, the binding of CpG-ODN and GpG-ODN was not restricted to TLR-9 as both ODNs also interacted with TLR-3, TLR-7, and TLR-8. Taken together, the data indicate that the protective mechanism of GpG-ODN treatment in the NZB/W model of lupus nephritis involves modulating T cell cytokine profiles and B lymphocyte activation through the inhibition of several TLRs, including TLR-7 and TLR-9. |
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Authors:
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Kareem L Graham; Lowen Y Lee; John P Higgins; Lawrence Steinman; Paul J Utz; Peggy P Ho |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Autoimmunity Volume: 43 ISSN: 1607-842X ISO Abbreviation: Autoimmunity Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-01 Completed Date: 2010-05-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8900070 Medline TA: Autoimmunity Country: England |
Other Details:
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Languages: eng Pagination: 140-55 Citation Subset: IM |
Affiliation:
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Department of Medicine, Stanford University School of Medicine, CA 94305, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / drug effects, immunology Enzyme-Linked Immunosorbent Assay Female Lupus Nephritis / immunology, prevention & control* Lymphocyte Activation / drug effects, immunology Mice Mice, Inbred C57BL Mice, Inbred NZB Oligodeoxyribonucleotides / immunology, pharmacology* T-Lymphocyte Subsets / drug effects, immunology T-Lymphocytes / drug effects, immunology Toll-Like Receptors / immunology* |
| Grant Support | |
ID/Acronym/Agency:
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AI10663-02/AI/NIAID NIH HHS; AI50854/AI/NIAID NIH HHS; AI50865/AI/NIAID NIH HHS; AR49328/AR/NIAMS NIH HHS; DK61934/DK/NIDDK NIH HHS; N01-HV-28183/HV/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CPG-oligonucleotide; 0/GpG-oligonucleotide; 0/Oligodeoxyribonucleotides; 0/Toll-Like Receptors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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