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Prostaglandin E2 and tumor necrosis factor alpha cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production.

Rieser C, Böck G, Klocker H, Bartsch G, Thurnher M - J. Exp. Med. (1997)

Bottom Line: Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS).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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University of Innsbruck, A-6020 Innsbruck, Austria.

ABSTRACT
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)-alpha to induce high levels of IL-12 production by DCs. Addition of TNF-alpha 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-alpha 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-alpha 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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T cell stimulatory capacity of DCs cultured with  PGE2. Day-5 DCs were recultured in the absence or presence  of PGE2 (10 μM), TNF-α  (1,000 U/ml), or PGE2 plus  TNF-α. After 48 h the cells were  washed, irradiated, and DCs were  used as stimulators of allogeneic  T cell proliferation. Proliferation  was monitored by measuring  [methyl-3H]thymidine uptake on  day 5 of coculture. Each value  represents the mean cpm of triplicate cultures with SD.
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Figure 5: T cell stimulatory capacity of DCs cultured with PGE2. Day-5 DCs were recultured in the absence or presence of PGE2 (10 μM), TNF-α (1,000 U/ml), or PGE2 plus TNF-α. After 48 h the cells were washed, irradiated, and DCs were used as stimulators of allogeneic T cell proliferation. Proliferation was monitored by measuring [methyl-3H]thymidine uptake on day 5 of coculture. Each value represents the mean cpm of triplicate cultures with SD.

Mentions: The formation of clusters serves to establish close contacts between DCs and T cells, thereby favoring TCR engagement and T cell activation (11). Fig. 5 shows that DCs treated with PGE2 and TNF-α also exhibited the highest capacity to stimulate allogeneic T cell proliferation. Treatment of DCs with either substance alone also enhanced T cell proliferation, but to a smaller extent (Fig. 5).


Prostaglandin E2 and tumor necrosis factor alpha cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production.

Rieser C, Böck G, Klocker H, Bartsch G, Thurnher M - J. Exp. Med. (1997)

T cell stimulatory capacity of DCs cultured with  PGE2. Day-5 DCs were recultured in the absence or presence  of PGE2 (10 μM), TNF-α  (1,000 U/ml), or PGE2 plus  TNF-α. After 48 h the cells were  washed, irradiated, and DCs were  used as stimulators of allogeneic  T cell proliferation. Proliferation  was monitored by measuring  [methyl-3H]thymidine uptake on  day 5 of coculture. Each value  represents the mean cpm of triplicate cultures with SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199106&req=5

Figure 5: T cell stimulatory capacity of DCs cultured with PGE2. Day-5 DCs were recultured in the absence or presence of PGE2 (10 μM), TNF-α (1,000 U/ml), or PGE2 plus TNF-α. After 48 h the cells were washed, irradiated, and DCs were used as stimulators of allogeneic T cell proliferation. Proliferation was monitored by measuring [methyl-3H]thymidine uptake on day 5 of coculture. Each value represents the mean cpm of triplicate cultures with SD.
Mentions: The formation of clusters serves to establish close contacts between DCs and T cells, thereby favoring TCR engagement and T cell activation (11). Fig. 5 shows that DCs treated with PGE2 and TNF-α also exhibited the highest capacity to stimulate allogeneic T cell proliferation. Treatment of DCs with either substance alone also enhanced T cell proliferation, but to a smaller extent (Fig. 5).

Bottom Line: Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS).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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University of Innsbruck, A-6020 Innsbruck, Austria.

ABSTRACT
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)-alpha to induce high levels of IL-12 production by DCs. Addition of TNF-alpha 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-alpha 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-alpha 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.

Show MeSH
Related in: MedlinePlus