| Systemic lupus erythematosus monocytes are less responsive to interleukin-10 in the presence of immune complexes. | |
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MedLine Citation:
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PMID: 20954190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic inflammatory disease characterized by autoantibody production and immune complex deposition. The level of interleukin-10 (IL-10), predominantly an antiinflammatory cytokine, is paradoxically elevated in patients with SLE. The aim of this study was to examine the hypothesis that the antiinflammatory function of IL-10 is impaired in monocytes from patients with SLE with long-term exposure to immune complexes. METHODS: CD14+ monocytes were isolated from healthy donors and patients with SLE. Cultured CD14+ cells were treated with heat-aggregated human IgG (325 μg/ml) in the presence or absence of IL-10 (20 ng/ml). To study gene expression, RNA was extracted 3 hours after treatment. To study cytokine production, supernatants were harvested after 8 hours. To study IL-10 signaling, cell lysates were obtained from CD14+ cells treated with human IgG (325 μg/ml) for 1 hour followed by IL-10 (20 ng/ml) treatment for 10 minutes. Western blot analysis was used to assess STAT-3 phosphorylation. All experiments were performed in pairs. RESULTS: When stimulated with human IgG, SLE monocytes produced more tumor necrosis factor α (TNFα) and IL-6 than did control cells. The suppressive effect of IL-10 on human IgG-induced TNFα and IL-6 production was lower in SLE monocytes compared with control monocytes, although IL-10 receptor expression was similar in SLE and control monocytes. Human IgG suppressed IL-10 receptor expression and altered IL-10 signaling in control monocytes. Like SLE monocytes, interferon-α (IFNα)-primed control monocytes stimulated with human IgG were also less responsive to IL-10. CONCLUSION: Human IgG and IFNα modulate IL-10 function. In SLE monocytes, which are considered to be IFNα primed and persistently exposed to immune complexes, responses to IL-10 are abnormal, limiting the antiinflammatory effect of this cytokine. |
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Authors:
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Weijia Yuan; Stephen J DiMartino; Patricia B Redecha; Lionel B Ivashkiv; Jane E Salmon |
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: Arthritis and rheumatism Volume: 63 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-04 Completed Date: 2011-01-28 Revised Date: 2012-03-08 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 212-8 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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Hospital for Special Surgery and Weill Cornell Medical College, New York, New York 10021, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigen-Antibody Complex
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immunology,
metabolism* Blotting, Western Cells, Cultured Cytokines / immunology, metabolism Female Gene Expression Humans Immunoglobulin G / immunology, metabolism, pharmacology Interleukin-10 / immunology, metabolism, pharmacology* Lupus Erythematosus, Systemic / immunology, metabolism* Male Monocytes / drug effects, immunology, metabolism* Phosphorylation RNA, Messenger / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI044938-13/AI/NIAID NIH HHS; R01 AI046712-11/AI/NIAID NIH HHS; R01 AI046712-12/AI/NIAID NIH HHS; R01 AI046712-13/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigen-Antibody Complex; 0/Cytokines; 0/Immunoglobulin G; 0/RNA, Messenger; 130068-27-8/Interleukin-10 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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