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Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis
Interleukin-10 (IL-10) is a potent deactivator of myeloid cells that limits the intensity and duration of immune and inflammatory responses. The activity of IL-10 can be suppressed during inflammation, infection, or after allogeneic tissue transplantation. We investigated whether inflammatory factor...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193912/ https://www.ncbi.nlm.nih.gov/pubmed/12782719 http://dx.doi.org/10.1084/jem.20021820 |
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author | Ji, Jong-Dae Tassiulas, Ioannis Park-Min, Kyung-Hyun Aydin, Ani Mecklenbräuker, Ingrid Tarakhovsky, Alexander Pricop, Luminita Salmon, Jane E. Ivashkiv, Lionel B. |
author_facet | Ji, Jong-Dae Tassiulas, Ioannis Park-Min, Kyung-Hyun Aydin, Ani Mecklenbräuker, Ingrid Tarakhovsky, Alexander Pricop, Luminita Salmon, Jane E. Ivashkiv, Lionel B. |
author_sort | Ji, Jong-Dae |
collection | PubMed |
description | Interleukin-10 (IL-10) is a potent deactivator of myeloid cells that limits the intensity and duration of immune and inflammatory responses. The activity of IL-10 can be suppressed during inflammation, infection, or after allogeneic tissue transplantation. We investigated whether inflammatory factors suppress IL-10 activity at the level of signal transduction. Out of many factors tested, only ligation of Fc receptors by immune complexes inhibited IL-10 activation of the Jak-Stat signaling pathway. IL-10 signaling was suppressed in rheumatoid arthritis joint macrophages that are exposed to immune complexes in vivo. Activation of macrophages with interferon-γ was required for Fc receptor–mediated suppression of IL-10 signaling, which resulted in diminished activation of IL-10–inducible genes and reversal of IL-10–dependent suppression of cytokine production. The mechanism of inhibition involved decreased cell surface IL-10 receptor expression and Jak1 activation and was dependent on protein kinase C delta. These results establish that IL-10 signaling is regulated during inflammation and identify Fc receptors and interferon-γ as important regulators of IL-10 activity. Generation of macrophages refractory to IL-10 can contribute to pathogenesis of inflammatory and infectious diseases characterized by production of interferon-γ and immune complexes. |
format | Text |
id | pubmed-2193912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21939122008-04-11 Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis Ji, Jong-Dae Tassiulas, Ioannis Park-Min, Kyung-Hyun Aydin, Ani Mecklenbräuker, Ingrid Tarakhovsky, Alexander Pricop, Luminita Salmon, Jane E. Ivashkiv, Lionel B. J Exp Med Article Interleukin-10 (IL-10) is a potent deactivator of myeloid cells that limits the intensity and duration of immune and inflammatory responses. The activity of IL-10 can be suppressed during inflammation, infection, or after allogeneic tissue transplantation. We investigated whether inflammatory factors suppress IL-10 activity at the level of signal transduction. Out of many factors tested, only ligation of Fc receptors by immune complexes inhibited IL-10 activation of the Jak-Stat signaling pathway. IL-10 signaling was suppressed in rheumatoid arthritis joint macrophages that are exposed to immune complexes in vivo. Activation of macrophages with interferon-γ was required for Fc receptor–mediated suppression of IL-10 signaling, which resulted in diminished activation of IL-10–inducible genes and reversal of IL-10–dependent suppression of cytokine production. The mechanism of inhibition involved decreased cell surface IL-10 receptor expression and Jak1 activation and was dependent on protein kinase C delta. These results establish that IL-10 signaling is regulated during inflammation and identify Fc receptors and interferon-γ as important regulators of IL-10 activity. Generation of macrophages refractory to IL-10 can contribute to pathogenesis of inflammatory and infectious diseases characterized by production of interferon-γ and immune complexes. The Rockefeller University Press 2003-06-02 /pmc/articles/PMC2193912/ /pubmed/12782719 http://dx.doi.org/10.1084/jem.20021820 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Ji, Jong-Dae Tassiulas, Ioannis Park-Min, Kyung-Hyun Aydin, Ani Mecklenbräuker, Ingrid Tarakhovsky, Alexander Pricop, Luminita Salmon, Jane E. Ivashkiv, Lionel B. Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis |
title | Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis |
title_full | Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis |
title_fullStr | Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis |
title_full_unstemmed | Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis |
title_short | Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis |
title_sort | inhibition of interleukin 10 signaling after fc receptor ligation and during rheumatoid arthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193912/ https://www.ncbi.nlm.nih.gov/pubmed/12782719 http://dx.doi.org/10.1084/jem.20021820 |
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