Differential regulation of CD4(+) T helper cell responses by curcumin in experimental autoimmune encephalomyelitis

Neuroscience Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN 46202, USA.
The Journal of nutritional biochemistry (Impact Factor: 3.79). 03/2012; 23(11):1498-507. DOI: 10.1016/j.jnutbio.2011.10.002
Source: PubMed


Nutraceuticals and phytochemicals are important regulators of human health and diseases. Curcumin is a polyphenolic phytochemical isolated from the rhizome of the plant Curcuma longa (turmeric) that has been traditionally used for the treatment of inflammation and wound healing for centuries. Systematic analyses have shown that curcumin exerts its beneficial effects through antioxidant, antiproliferative and anti-inflammatory properties. We and others have shown earlier that curcumin ameliorates experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis. In this study, we show that C57BL/6 mice induced to develop EAE express elevated levels of interferon (IFN) γ and interleukin (IL)-17 in the central nervous system (CNS) and lymphoid organs that decreased significantly following in vivo treatment with curcumin. The EAE mice also showed elevated expression of IL-12 and IL-23 that decreased after treatment with curcumin. Ex vivo and in vitro treatment with curcumin resulted in a dose-dependent decrease in the secretion of IFNγ, IL-17, IL-12 and IL-23 in culture. The inhibition of EAE by curcumin was also associated with an up-regulation of IL-10, peroxisome proliferator activated receptor γ and CD4(+)CD25(+)Foxp3(+) Treg cells in the CNS and lymphoid organs. These findings highlight that curcumin differentially regulates CD4(+) T helper cell responses in EAE.

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    • " domesticus ) challenged with Eimeria tenella ( Lee et al . , 2011 ) . Curcumin alone has also been shown to increase mouse CD4 + cells in the spleen ( Yasni et al . , 1993 ) and intestinal mucosa ( Churchill et al . , 2000 ) . In experimental autoimmune encephalomyelitis , curcumin increased mouse CD4 + CD25 + T - regulatory cells in the spleen ( Kanakasabai et al . , 2012 ) . However , curcumin has also been shown to inhibit the expansion of splenic CD4 + cells and their expression of CD25 in vitro ( For - ward et al . , 2011 ) . In the present study , it was not determined if the CD4 + CD25 + population were regula - tory T cells . When CD4 T lymphocytes are activated , they produce cytokines that activ"
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    ABSTRACT: This study investigated the effect of phytonutrients (PN) supplied postruminally on nutrient utilization, gut microbial ecology, immune response, and productivity of lactating dairy cows. Eight ruminally cannulated Holstein cows were used in a replicated 4 × 4 Latin square. Experimental periods lasted 23 d, including 14-d washout and 9-d treatment periods. Treatments were control (no PN) and daily doses of 2 g/cow of either curcuma oleoresin (curcumin), garlic extract (garlic), or capsicum oleoresin (capsicum). Phytonutrients were pulse-dosed into the abomasum of the cows, through the rumen cannula, 2 h after feeding during the last 9 d of each experimental period. Dry matter intake was not affected by PN, although it tended to be lower for the garlic treatment compared with the control. Milk yield was decreased (2.2 kg/d) by capsicum treatment compared with the control. Feed efficiency, milk composition, milk fat and protein yields, milk N efficiency, and 4.0% fat-corrected milk yield were not affected by treatment. Rumen fermentation variables, apparent total-tract digestibility of nutrients, N excretion with feces and urine, and diversity of fecal bacteria were also not affected by treatment. Phytonutrients had no effect on blood chemistry, but the relative proportion of lymphocytes was increased by the capsicum treatment compared with the control. All PN increased the proportion of total CD4(+) cells and total CD4(+) cells that co-expressed the activation status signal and CD25 in blood. The percentage of peripheral blood mononuclear cells (PBMC) that proliferated in response to concanavalin A and viability of PBMC were not affected by treatment. Cytokine production by PBMC was not different between control and PN. Expression of mRNA in liver for key enzymes in gluconeogenesis, fatty acid oxidation, and response to reactive oxygen species were not affected by treatment. No difference was observed due to treatment in the oxygen radical absorbance capacity of blood plasma but, compared with the control, garlic treatment increased 8-isoprostane levels. Overall, the PN used in this study had subtle or no effects on blood cells and blood chemistry, nutrient digestibility, and fecal bacterial diversity, but appeared to have an immune-stimulatory effect by activating and inducing the expansion of CD4 cells in dairy cows. Capsicum treatment decreased milk yield, but this and other effects observed in this study should be interpreted with caution because of the short duration of treatment.
    Journal of Dairy Science 10/2013; 96(12). DOI:10.3168/jds.2013-7089 · 2.57 Impact Factor
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    • "Information regarding the impact of spices on CD4 subpopulation is limited. Dietary curcumin was shown to ameliorate EAE in rats through inhibition of Th17 response [49] and in mice through inhibition of Th1/Th17 responses and enhancement of Th2/Treg responses [50]. Taken together, these results indicate a potential area for future studies to explore: whether the beneficial effect of CR on autoimmune diseases is mediated through its effect on CD4+ T cell differentiation and further, whether CR interacts with spice compound supplementation to mutually potentiate their respective effectiveness. "
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    ABSTRACT: Background Obesity is associated with low-grade inflammation and impaired immune response. Caloric restriction (CR) has been shown to inhibit inflammatory response and enhance cell-mediated immune function. Curcumin, the bioactive phenolic component of turmeric spice, is proposed to have anti-obesity and anti-inflammation properties while piperine, another bioactive phenolic compound present in pepper spice, can enhance the bioavailability and efficacy of curcumin. This study sought to determine if curcumin could potentiate CR’s beneficial effect on immune and inflammatory responses in obesity developed in mice by feeding high-fat diet (HFD). Methods Mice were fed a HFD for 22 wk and then randomized into 5 groups: one group remained on HFD ad libitum and the remaining 4 groups were fed a 10% CR (reduced intake of HFD by 10% but maintaining the same levels of micronutrients) in the presence or absence of curcumin and/or piperine for 5 wk, after which CR was increased to 20% for an additional 33 wk. At the end of the study, mice were sacrificed, and spleen cells were isolated. Cells were stimulated with T cell mitogens, anti-CD3/CD28 antibodies, or lipopolysaccharide to determine T cell proliferation, cytokine production, and CD4+ T cell subpopulations. Results Compared to HFD control group, all CR mice, regardless of the presence of curcumin and/or piperine, had lower body weight and fat mass, lower levels of blood glucose and insulin, and fewer total spleen cells but a higher percentage of CD4+ T cells. Additionally, they demonstrated lower production of pro-inflammatory cytokines IL-1β and TNF-α, a trend toward lower IL-6, and lower production of PGE2, a lipid molecule with pro-inflammatory and T cell-suppressive properties. Mice with CR alone had higher splenocyte proliferation and IL-2 production, but this effect of CR was diminished by spice supplementation. CR alone or in combination with spice supplementation had no effect on production of cytokines IL-4, IL-10, IFN-γ, and IL-17, or the proportion of different CD4+ T cell subsets. Conclusion CR on an HFD favorably impacts both metabolic and immune/inflammatory profiles; however, the presence of curcumin and/or piperine does not amplify CR’s beneficial effects.
    Nutrition & Metabolism 03/2013; 10(1):29. DOI:10.1186/1743-7075-10-29 · 3.26 Impact Factor
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    • "Finally, in an in vitro and in vivo investigation, curcumin delivered to mice significantly attenuated LPS-induced increases in IDO expression in bone marrow-derived dendritic cells (Jung et al., 2010). Further evidence of curcumin's immuno-modulating effects are demonstrated by its ability to lower Th-17 autoimmune responses (Xie et al., 2009; Kanakasabai et al., 2012), which have recently been shown to be upregulated in major depression (Chen et al., 2011). Curcumin also decreases the expression of Th-1 cytokines (e.g. "
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    ABSTRACT: Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.
    Journal of Psychopharmacology 10/2012; 26(12). DOI:10.1177/0269881112458732 · 3.59 Impact Factor
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