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9V
2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation1
*
Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461;
Laboratory of Neuroimmunology and
Institute of Neurobiology, Instituto di Ricovero e Cura a Carattere Scientifico Santa Lucia, Rome, Italy; and
Department of Neuroscience, Second University of Rome Tor Vergata, Rome, Italy
Curcumin, in addition to its role as a spice, has been used for
centuries to treat inflammatory disorders. Although the mechanism of
action remains unclear, it has been shown to inhibit the activation of
NF-
B and AP-1, transcription factors required for induction of many
proinflammatory mediators. Due to its low toxicity it is currently
under consideration as a broad anti-inflammatory, anti-tumor
cell agent. In this study we investigated whether curcumin inhibited
the response of 
T cells to protease-resistant phosphorylated
derivatives found in the cell wall of many pathogens. The results
showed that curcumin levels 
30 µM profoundly inhibited isopentenyl
pyrophosphate-induced release of the chemokines macrophage inflammatory
protein-1
and -1
and RANTES. Curcumin also blocked isopentenyl
pyrophosphate-induced activation of NF-B and AP-1. Commencing around
16 h, treatment with curcumin lead to the induction of cell death
that could not be reversed by APC, IL-15, or IL-2. This cytotoxicity
was associated with increased annexin V reactivity, nuclear expression
of active caspase-3, cleavage of poly(ADP-ribose) polymerase,
translocation of apoptosis-inducing factor to the nucleus, and
morphological evidence of nuclear disintegration. However, curcumin led
to only large scale DNA chromatolysis, as determined by a combination
of TUNEL staining and pulse-field and agarose gel electrophoresis,
suggesting a predominantly apoptosis-inducing factor-mediated cell
death process. We conclude that T cells activated by these
ubiquitous Ags are highly sensitive to curcumin, and that this effect
may contribute to the anti-inflammatory properties of this
compound.
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  L. Chen, M. T. Cencioni, D. F. Angelini, G. Borsellino, L. Battistini, and C. F. Brosnan Transcriptional Profiling of {gamma}{delta} T Cells Identifies a Role for Vitamin D in the Immunoregulation of the V{gamma}9V{delta}2 Response to Phosphate-Containing Ligands J. Immunol., May 15, 2005; 174(10): 6144 - 6152. [Abstract] [Full Text] [PDF]
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B. Cipriani, H. Knowles, L. Chen, L. Battistini, and C. F. Brosnan Involvement of Classical and Novel Protein Kinase C Isoforms in the Response of Human V{gamma}9V{delta}2 T Cells to Phosphate Antigens J. Immunol., November 15, 2002; 169(10): 5761 - 5770. [Abstract] [Full Text] [PDF]
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