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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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Curcumin modulation in multiple sclerosis (MS) patients. PBMC's were isolated from MS patients (n = 4) and as with the in vitro samples were stimulated with either IFN-β (10 ng/ml) or IL-12 (100 ng/ml). Both induced pSTAT4 expression (unshaded 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.(Shaded curve on each graph represents unstimulated cells). IFN-β and IL-10 levels were measured using a solid-phase sandwich ELISA. IFN-β (10 ng/ml) induces IL-10 production in human T cells (A). IL-10 production is enhanced by prior exposure to curcumin (20 μg/ml). IL-12 (0.1 μg/ml) induces IFN-γ production in human T cells (B). Pre-treatment of these cells with curcumin (20 μg/ml) reduces this induction. The duration of exposure of the cells to IFN-β, IL-12 and curcumin was 18 hrs.
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fig07: Curcumin modulation in multiple sclerosis (MS) patients. PBMC's were isolated from MS patients (n = 4) and as with the in vitro samples were stimulated with either IFN-β (10 ng/ml) or IL-12 (100 ng/ml). Both induced pSTAT4 expression (unshaded 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.(Shaded curve on each graph represents unstimulated cells). IFN-β and IL-10 levels were measured using a solid-phase sandwich ELISA. IFN-β (10 ng/ml) induces IL-10 production in human T cells (A). IL-10 production is enhanced by prior exposure to curcumin (20 μg/ml). IL-12 (0.1 μg/ml) induces IFN-γ production in human T cells (B). Pre-treatment of these cells with curcumin (20 μg/ml) reduces this induction. The duration of exposure of the cells to IFN-β, IL-12 and curcumin was 18 hrs.

Mentions: To determine whether the immunomodulatory effects of curcumin are similar in T cells from normal donors and patients with MS, we performed the above studies on T cells from PBMC of MS patients. We showed the same effects on IFN-β and IL-12 induction of cytokines, STAT4 phosphorylation (Fig. 7A and B) and IL-10 and IFN-γ modulation (see Fig. 7C and D).


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)

Curcumin modulation in multiple sclerosis (MS) patients. PBMC's were isolated from MS patients (n = 4) and as with the in vitro samples were stimulated with either IFN-β (10 ng/ml) or IL-12 (100 ng/ml). Both induced pSTAT4 expression (unshaded 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.(Shaded curve on each graph represents unstimulated cells). IFN-β and IL-10 levels were measured using a solid-phase sandwich ELISA. IFN-β (10 ng/ml) induces IL-10 production in human T cells (A). IL-10 production is enhanced by prior exposure to curcumin (20 μg/ml). IL-12 (0.1 μg/ml) induces IFN-γ production in human T cells (B). Pre-treatment of these cells with curcumin (20 μg/ml) reduces this induction. The duration of exposure of the cells to IFN-β, IL-12 and curcumin was 18 hrs.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4401279&req=5

fig07: Curcumin modulation in multiple sclerosis (MS) patients. PBMC's were isolated from MS patients (n = 4) and as with the in vitro samples were stimulated with either IFN-β (10 ng/ml) or IL-12 (100 ng/ml). Both induced pSTAT4 expression (unshaded 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.(Shaded curve on each graph represents unstimulated cells). IFN-β and IL-10 levels were measured using a solid-phase sandwich ELISA. IFN-β (10 ng/ml) induces IL-10 production in human T cells (A). IL-10 production is enhanced by prior exposure to curcumin (20 μg/ml). IL-12 (0.1 μg/ml) induces IFN-γ production in human T cells (B). Pre-treatment of these cells with curcumin (20 μg/ml) reduces this induction. The duration of exposure of the cells to IFN-β, IL-12 and curcumin was 18 hrs.
Mentions: To determine whether the immunomodulatory effects of curcumin are similar in T cells from normal donors and patients with MS, we performed the above studies on T cells from PBMC of MS patients. We showed the same effects on IFN-β and IL-12 induction of cytokines, STAT4 phosphorylation (Fig. 7A and B) and IL-10 and IFN-γ modulation (see Fig. 7C and D).

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