| Production of TNF-α in Macrophages Activated by T Cells, Compared with Lipopolysaccharide, Uses Distinct IL-10-Dependent Regulatory Mechanism. | |
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MedLine Citation:
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PMID: 22219323 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Previously, we demonstrated that spontaneous TNF-α production by macrophages in rheumatoid arthritis (RA) synovial tissue is largely driven by contact-dependent activation with T cells in that tissue. Whereas abundant IL-10 is present in these RA synovial cultures, it does not adequately control the production of TNF-α. In this study, we have compared the mechanisms involved in IL-10-mediated TNF-α regulation in LPS-stimulated macrophages with macrophages stimulated with activated T cells. We confirm that in LPS-stimulated macrophages the 3' enhancer region of tnf is essential for tnf transcription, and its regulation by IL-10 is dominated by a STAT3-dependent pathway. However, in contrast, we have found that tnf transcription in macrophages stimulated by activated T cells or by RA synovial T cells does not require the 3' enhancer region of tnf, and that its regulation by IL-10 is subsequently altered and clearly is not mediated by a dominant STAT3 pathway. These observations have very important implications for our understanding as to how IL-10 regulates TNF-α production at sites of chronic inflammation, such as the synovial tissue of patients with RA. Furthermore, these distinct IL-10 mechanisms will have bearing upon the identification of potential therapeutic targets in RA synovial macrophages where the activation stimulus is clearly not LPS. |
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Authors:
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Gideon Agbanoma; Ching Li; Darren Ennis; Andrew C Palfreeman; Lynn M Williams; Fionula M Brennan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-4 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Kennedy Institute of Rheumatology Division, University of Oxford, London W6 8LH, United Kingdom (formerly until August 1, 2011, Kennedy Institute of Rheumatology Division, Imperial College London, London W6 8LH). |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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