Curcumin Suppresses T Cell Activation by Blocking Ca2+ Mobilization and Nuclear Factor of Activated T Cells (NFAT) Activation

Kliem, Christian; Merling, Anette; Giaisi, Marco; Köhler, Rebecca; Krammer, Peter H.; Li‐Weber, Min

doi:10.1074/jbc.m111.318733

Cited by 46 publications

(24 citation statements)

References 42 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may reflect a suppressive effect of curcumin and piperine on T cell-mediated functions as reported in several previous studies [40-44]. For example, it has been shown that dietary curcumin in mice suppresses CD4 + T cell proliferation and IL-2 production [43] while in vitro curcumin supplementation inhibits T cell activation [44], human peripheral blood mononuclear cell proliferation and IL-2 production [40,42], and IL-2 synthesis as well as IL-2 signaling in mouse CD4+ T cells [41]. Although little information is available for piperine in this regard, some studies have indeed suggested that piperine may inhibit T cell-related functions [19,45].…”

Section: Discussionsupporting

confidence: 65%

Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit

Wang

Vanegas

et al. 2013

Nutr Metab (Lond)

View full text Add to dashboard Cite

BackgroundObesity 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).MethodsMice 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.ResultsCompared 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.ConclusionCR 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.

show abstract

Section: Discussionsupporting

confidence: 65%

Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit

Wang

Vanegas

et al. 2013

Nutr Metab (Lond)

View full text Add to dashboard Cite

show abstract

“…It is also noteworthy that the mode of sustained Ca 2+ cyt rise in CUR+CA-treated AML cells is distinct from those proposed for polyphenols. Specifically, elevation of Ca 2+ cyt did not involve the previously reported modulation of store-operated [45] or voltage-dependent [46] Ca 2+ entry because the removal of extracellular Ca 2+ did not affect the extent of CUR+CA-induced apoptosis (Figure 3A). Likewise, accumulation of Ca 2+ cyt did not result solely from massive Ca 2+ ER release despite the fact that CUR is a known inhibitor of SERCA [43].…”

Section: Discussionmentioning

confidence: 62%

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

et al. 2016

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by extremely heterogeneous molecular and biologic abnormalities that hamper the development of effective targeted treatment modalities. While AML cells are highly sensitive to cytotoxic Ca2+ overload, the feasibility of Ca2+- targeted therapy of this disease remains unclear. Here, we show that apoptotic response of AML cells to the synergistically acting polyphenols curcumin (CUR) and carnosic acid (CA), combined at low, non-cytotoxic doses of each compound was mediated solely by disruption of cellular Ca2+ homeostasis. Specifically, activation of caspase cascade in CUR+CA-treated AML cells resulted from sustained elevation of cytosolic Ca2+ (Ca2+cyt) and was not preceded by endoplasmic reticulum stress or mitochondrial damage. The CUR+CA-induced Ca2+cyt rise did not involve excessive influx of extracellular Ca2+ but, rather, occurred due to massive Ca2+ release from intracellular stores concomitant with inhibition of Ca2+cyt extrusion through the plasma membrane. Notably, the CUR+CA combination did not alter Ca2+ homeostasis and viability in non-neoplastic hematopoietic cells, suggesting its cancer-selective action. Most importantly, co-administration of CUR and CA to AML-bearing mice markedly attenuated disease progression in two animal models. Collectively, our results provide the mechanistic and translational basis for further characterization of this combination as a prototype of novel Ca2+-targeted pharmacological tools for the treatment of AML.

show abstract

“…Previous studies have found that curcumin may inhibit cytokine expression and reduce inflammation, as well as inhibit the secretion of TGF-β (34). These studies suggested that curcumin may be beneficial during fibrosis, and as multiple pathways, including inflammation, TGF-β and KL have been demonstrated to be involved in kidney fibrosis the current study investigated whether curcumin alleviates fibrosis through a KL-mediated pathway, while it is possible that other pathways are involved.…”

Section: Discussionmentioning

confidence: 95%

Curcumin attenuates cyclosporine A-induced renal fibrosis by inhibiting hypermethylation of the klotho promoter

Mou

Feng

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Chronic kidney disease is increasingly considered to be a worldwide public health problem and usually leads to renal fibrosis. In the present study, curcumin, a polyphenol pigment extracted from turmeric, was demonstrated to exert protective effects on renal fibrosis via the suppression of transforming growth factor‑β (TGF‑β) downstream signaling, such as plasminogen activator inhibitor‑1 (PAI‑1), α‑smooth muscle actin (α‑SMA) and collagen I (Col I) downregulation. The present findings demonstrate that curcumin exerted a protective effect on cyclosporine A‑induced renal fibrosis via a klotho (KL)‑dependent mechanism, which inhibits the TGF‑β signaling pathway. Further research indicated that curcumin induced KL expression in HK‑2 tubular epithelial cells by inhibiting CpG hypermethylation in the KL promoter, which mediates the loss of expression in cells. Methylation‑specific polymerase chain reaction (PCR) combined with bisulfite sequencing identified numerous key CpG sites, such as 249, 240 and 236, whose methylation statuses are important for KL expression. A PCR reporter assay was utilized to further confirm these findings. In addition, the effects of curcumin on the regulation of DNA methyltransferase 1 (Dnmt1) expression were evaluated, and the data suggest that curcumin inhibits Dnmt1 expression and restricts CpG hypermethylation. Thus, the current study reveals that curcumin attenuated renal fibrosis by suppressing CpG methylation in the KL promoter, thus inducing KL expression, which inhibited TGF‑β signaling, which may provide a novel therapeutic approach for the treatment of renal fibrosis.

show abstract

Curcumin Suppresses T Cell Activation by Blocking Ca2+ Mobilization and Nuclear Factor of Activated T Cells (NFAT) Activation

Cited by 46 publications

References 42 publications

Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit

Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

Curcumin attenuates cyclosporine A-induced renal fibrosis by inhibiting hypermethylation of the klotho promoter

Contact Info

Product

Resources

About