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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...

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Autores principales: Ji, Jong-Dae, Tassiulas, Ioannis, Park-Min, Kyung-Hyun, Aydin, Ani, Mecklenbräuker, Ingrid, Tarakhovsky, Alexander, Pricop, Luminita, Salmon, Jane E., Ivashkiv, Lionel B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
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.
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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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