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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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Modulation of IL-12 induced IFN-γ by curcumin. Quantitative real-time PCR and flow cytometry were used to assess IFN-γ mRNA and protein expression, respectively, in PHA/IL-2 T cell blasts. IL-12 (100 ng/ml) increased IFN-g production, however, pre-treatment of these cells with curcumin (20 μg/ml) reduced this induction (A). IL-12 stimulation increased IFN-γprotein expression (shaded curve) compared to unstimulated cells (US), an induction that was reduced by prior treatment of the cells with curcumin (20 μg/ml) (unshaded curve) (B).
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fig05: Modulation of IL-12 induced IFN-γ by curcumin. Quantitative real-time PCR and flow cytometry were used to assess IFN-γ mRNA and protein expression, respectively, in PHA/IL-2 T cell blasts. IL-12 (100 ng/ml) increased IFN-g production, however, pre-treatment of these cells with curcumin (20 μg/ml) reduced this induction (A). IL-12 stimulation increased IFN-γprotein expression (shaded curve) compared to unstimulated cells (US), an induction that was reduced by prior treatment of the cells with curcumin (20 μg/ml) (unshaded curve) (B).

Mentions: In this study, both IFN-β and IFN-α are shown to induce IL-10 production in T cells (Fig. 4), which was enhanced by prior treatment with curcumin (P < 0.05). These results were confirmed by ELISA (Fig. 6A). IL-12 dependent production of IFN-γ is important in the generation of a cell-mediated immune response. Here, we show increased IFN-γ mRNA production by IL-12 in human T cells. However, pre-treatment of these cells with curcumin reduced this induction (Fig. 5A, P < 0.05). We also investigated whether IL-12-induced IFN-γ protein production was also decreased by prior exposure to curcumin; the results were consistent with what we observed at the mRNA level. IL-12 stimulation increased IFN-γ protein expression compared to unstimulated cells, an induction that was reduced by prior treatment of the cells with curcumin (Fig. 5B). These results were confirmed using ELISA (Fig. 6B).


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 IL-12 induced IFN-γ by curcumin. Quantitative real-time PCR and flow cytometry were used to assess IFN-γ mRNA and protein expression, respectively, in PHA/IL-2 T cell blasts. IL-12 (100 ng/ml) increased IFN-g production, however, pre-treatment of these cells with curcumin (20 μg/ml) reduced this induction (A). IL-12 stimulation increased IFN-γprotein expression (shaded curve) compared to unstimulated cells (US), an induction that was reduced by prior treatment of the cells with curcumin (20 μg/ml) (unshaded curve) (B).
© Copyright Policy
Related In: Results  -  Collection

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

fig05: Modulation of IL-12 induced IFN-γ by curcumin. Quantitative real-time PCR and flow cytometry were used to assess IFN-γ mRNA and protein expression, respectively, in PHA/IL-2 T cell blasts. IL-12 (100 ng/ml) increased IFN-g production, however, pre-treatment of these cells with curcumin (20 μg/ml) reduced this induction (A). IL-12 stimulation increased IFN-γprotein expression (shaded curve) compared to unstimulated cells (US), an induction that was reduced by prior treatment of the cells with curcumin (20 μg/ml) (unshaded curve) (B).
Mentions: In this study, both IFN-β and IFN-α are shown to induce IL-10 production in T cells (Fig. 4), which was enhanced by prior treatment with curcumin (P < 0.05). These results were confirmed by ELISA (Fig. 6A). IL-12 dependent production of IFN-γ is important in the generation of a cell-mediated immune response. Here, we show increased IFN-γ mRNA production by IL-12 in human T cells. However, pre-treatment of these cells with curcumin reduced this induction (Fig. 5A, P < 0.05). We also investigated whether IL-12-induced IFN-γ protein production was also decreased by prior exposure to curcumin; the results were consistent with what we observed at the mRNA level. IL-12 stimulation increased IFN-γ protein expression compared to unstimulated cells, an induction that was reduced by prior treatment of the cells with curcumin (Fig. 5B). These results were confirmed using ELISA (Fig. 6B).

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