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Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production

Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investiga...

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Autores principales: Rieser, Claudia, Böck, Günther, Klocker, Helmut, Bartsch, Georg, Thurnher, Martin
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199106/
https://www.ncbi.nlm.nih.gov/pubmed/9348319
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author Rieser, Claudia
Böck, Günther
Klocker, Helmut
Bartsch, Georg
Thurnher, Martin
author_facet Rieser, Claudia
Böck, Günther
Klocker, Helmut
Bartsch, Georg
Thurnher, Martin
author_sort Rieser, Claudia
collection PubMed
description Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-α to induce high levels of IL-12 production by DCs. Addition of TNF-α in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-α efficiently silenced mannose receptor–mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-α were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs.
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spelling pubmed-21991062008-04-16 Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production Rieser, Claudia Böck, Günther Klocker, Helmut Bartsch, Georg Thurnher, Martin J Exp Med Brief Definitive Report Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-α to induce high levels of IL-12 production by DCs. Addition of TNF-α in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-α efficiently silenced mannose receptor–mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-α were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs. The Rockefeller University Press 1997-11-03 /pmc/articles/PMC2199106/ /pubmed/9348319 Text en 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 Brief Definitive Report
Rieser, Claudia
Böck, Günther
Klocker, Helmut
Bartsch, Georg
Thurnher, Martin
Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production
title Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production
title_full Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production
title_fullStr Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production
title_full_unstemmed Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production
title_short Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production
title_sort prostaglandin e2 and tumor necrosis factor α cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199106/
https://www.ncbi.nlm.nih.gov/pubmed/9348319
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