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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3 November 1997
Brief Definitive Report|
November 03 1997
Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production
Claudia Rieser,
Claudia Rieser
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
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Günther Böck,
Günther Böck
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
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Helmut Klocker,
Helmut Klocker
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
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Georg Bartsch,
Georg Bartsch
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
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Martin Thurnher
Martin Thurnher
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
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Claudia Rieser
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
Günther Böck
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
Helmut Klocker
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
Georg Bartsch
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
Martin Thurnher
From the *Department of Urology, and the ‡Institute for General and Experimental Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
Address correspondence to Dr. Martin Thurnher, The Department of Urology, Anichstrasse 35, 6020 Innsbruck, Austria. FAX: 43-512-504-4817; E-mail: [email protected]
Received:
July 21 1997
Revision Received:
September 02 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (9): 1603–1608.
Article history
Received:
July 21 1997
Revision Received:
September 02 1997
Citation
Claudia Rieser, Günther Böck, Helmut Klocker, Georg Bartsch, Martin Thurnher; Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production . J Exp Med 3 November 1997; 186 (9): 1603–1608. doi: https://doi.org/10.1084/jem.186.9.1603
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