Abstract
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-κB 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 γδ 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-1α and -1β and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-κB 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 γδ 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3454-3462 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 167 |
| Issue number | 6 |
| Publication status | Published - Sep 15 2001 |
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ASJC Scopus subject areas
- Immunology
Cite this
Curcumin inhibits activation of Vγ9Vδ2 T cells by phosphoantigens and induces apoptosis involving apoptosis-inducing factor and large scale DNA fragmentation. / Cipriani, B.; Borsellino, G.; Knowles, H.; Tramonti, D.; Cavaliere, F.; Bernardi, G.; Battistini, L.; Brosnan, C. F.
In: Journal of Immunology, Vol. 167, No. 6, 15.09.2001, p. 3454-3462.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Curcumin inhibits activation of Vγ9Vδ2 T cells by phosphoantigens and induces apoptosis involving apoptosis-inducing factor and large scale DNA fragmentation
AU - Cipriani, B.
AU - Borsellino, G.
AU - Knowles, H.
AU - Tramonti, D.
AU - Cavaliere, F.
AU - Bernardi, G.
AU - Battistini, L.
AU - Brosnan, C. F.
PY - 2001/9/15
Y1 - 2001/9/15
N2 - 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-κB 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 γδ 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-1α and -1β and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-κB 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 γδ 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.
AB - 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-κB 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 γδ 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-1α and -1β and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-κB 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 γδ 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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UR - http://www.scopus.com/inward/citedby.url?scp=0035884995&partnerID=8YFLogxK
M3 - Article
C2 - 11544338
AN - SCOPUS:0035884995
VL - 167
SP - 3454
EP - 3462
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -