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Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells.

Fahey AJ, Adrian Robins R, Constantinescu CS - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta.Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation.Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Neurology, University of Nottingham, Nottingham, UK.

ABSTRACT
Curcumin is a polyphenol derived from the dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties. Curcumin has been shown to exhibit an inhibitory effect on the production of inflammatory cytokines by human monocytes and has inhibited the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in association with a decrease in interleukin 12 (IL-12) production and signal transducer and activator of transcription 4 (STAT4) activation. The type I interferon (IFN) IFN-has the ability to suppress IL-12. Both IL-12 and IFN-alpha/beta signal through the activation by phosphorylation of STAT4. Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta. We report that curcumin decreases IL-12-induced STAT4 phosphorylation, IFN-gamma production, and IL-12 Rbeta1 and beta2 expression. IFN-beta-induced STAT4 phosphorylation, IL-10 production and IFN receptor (IFNAR) subunits 1 and 2 expression were enhanced by curcumin. Curcumin increased IFN-alpha-induced IL-10 and IFNAR1 expression. Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation. Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

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Related in: MedlinePlus

Modulation of pSTAT4 by curcumin. IFN-β (10 ng/ml), IFN-αl (10 ng/ml) and IL-12 (100 ng/ml) induced pSTAT4 expression (shaded curve on each graph). Prior incubation with curcumin (20 μg/ml) and then IFN-β resulted in an increase in pSTAT4 generation, whilst prior stimulation with curcumin (20 μg/ml) followed by incubation with IL-12 resulted in a decrease in pSTAT4 generation. Similar pSTAT4 generation was induced with both curcumin and then IFN-α and IFN-α alone. Dotted line on each graph represents unstimulated cells). Representative results of four independent experiments.
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fig01: Modulation of pSTAT4 by curcumin. IFN-β (10 ng/ml), IFN-αl (10 ng/ml) and IL-12 (100 ng/ml) induced pSTAT4 expression (shaded curve on each graph). Prior incubation with curcumin (20 μg/ml) and then IFN-β resulted in an increase in pSTAT4 generation, whilst prior stimulation with curcumin (20 μg/ml) followed by incubation with IL-12 resulted in a decrease in pSTAT4 generation. Similar pSTAT4 generation was induced with both curcumin and then IFN-α and IFN-α alone. Dotted line on each graph represents unstimulated cells). Representative results of four independent experiments.

Mentions: We examined whether curcumin affected IFN-β, IFN-α or IL-12-induced STAT4 phosphorylation. As shown in Figure 1, exposure to IFN-β, IFN-α or IL-12 resulted in increased pSTAT4 generation when compared to unstimulated cells. However, pre-treatment of the cells with curcumin produced contrasting results depending on whether the cells were subsequently exposed to IFN-β, IFN-α or IL-12. Pre-incubation with curcumin and then IFN-γ resulted in an increase in pSTAT4 generation (Fig. 1), whilst prior treatment with curcumin followed by IFN-γ resulted with similar pSTAT4 generation compared with IFN-γ alone. However, prior treatment with curcumin resulted in a decrease in pSTAT4 generation (Fig. 1).


Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells.

Fahey AJ, Adrian Robins R, Constantinescu CS - J. Cell. Mol. Med. (2007 Sep-Oct)

Modulation of pSTAT4 by curcumin. IFN-β (10 ng/ml), IFN-αl (10 ng/ml) and IL-12 (100 ng/ml) induced pSTAT4 expression (shaded curve on each graph). Prior incubation with curcumin (20 μg/ml) and then IFN-β resulted in an increase in pSTAT4 generation, whilst prior stimulation with curcumin (20 μg/ml) followed by incubation with IL-12 resulted in a decrease in pSTAT4 generation. Similar pSTAT4 generation was induced with both curcumin and then IFN-α and IFN-α alone. Dotted line on each graph represents unstimulated cells). Representative results of four independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401279&req=5

fig01: Modulation of pSTAT4 by curcumin. IFN-β (10 ng/ml), IFN-αl (10 ng/ml) and IL-12 (100 ng/ml) induced pSTAT4 expression (shaded curve on each graph). Prior incubation with curcumin (20 μg/ml) and then IFN-β resulted in an increase in pSTAT4 generation, whilst prior stimulation with curcumin (20 μg/ml) followed by incubation with IL-12 resulted in a decrease in pSTAT4 generation. Similar pSTAT4 generation was induced with both curcumin and then IFN-α and IFN-α alone. Dotted line on each graph represents unstimulated cells). Representative results of four independent experiments.
Mentions: We examined whether curcumin affected IFN-β, IFN-α or IL-12-induced STAT4 phosphorylation. As shown in Figure 1, exposure to IFN-β, IFN-α or IL-12 resulted in increased pSTAT4 generation when compared to unstimulated cells. However, pre-treatment of the cells with curcumin produced contrasting results depending on whether the cells were subsequently exposed to IFN-β, IFN-α or IL-12. Pre-incubation with curcumin and then IFN-γ resulted in an increase in pSTAT4 generation (Fig. 1), whilst prior treatment with curcumin followed by IFN-γ resulted with similar pSTAT4 generation compared with IFN-γ alone. However, prior treatment with curcumin resulted in a decrease in pSTAT4 generation (Fig. 1).

Bottom Line: Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta.Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation.Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Neurology, University of Nottingham, Nottingham, UK.

ABSTRACT
Curcumin is a polyphenol derived from the dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties. Curcumin has been shown to exhibit an inhibitory effect on the production of inflammatory cytokines by human monocytes and has inhibited the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in association with a decrease in interleukin 12 (IL-12) production and signal transducer and activator of transcription 4 (STAT4) activation. The type I interferon (IFN) IFN-has the ability to suppress IL-12. Both IL-12 and IFN-alpha/beta signal through the activation by phosphorylation of STAT4. Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta. We report that curcumin decreases IL-12-induced STAT4 phosphorylation, IFN-gamma production, and IL-12 Rbeta1 and beta2 expression. IFN-beta-induced STAT4 phosphorylation, IL-10 production and IFN receptor (IFNAR) subunits 1 and 2 expression were enhanced by curcumin. Curcumin increased IFN-alpha-induced IL-10 and IFNAR1 expression. Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation. Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

Show MeSH
Related in: MedlinePlus