Curcumin inhibits activation of V gamma 9V delta 2 T cells by phosphoantigens and induces apoptosis involving apoptosis-inducing factor and large scale DNA fragmentation

Curcumin, in addition to its role as a spice, has been used for centuries t o treat inflammatory disorders. Although the mechanism of action remains un clear, it has been shown to inhibit the activation of NF-kappaB and AP-1, t ranscription factors required for induction of many proinflammatory mediato rs. Due to its low toxicity it is currently under consideration as a broad antiinflammatory, anti-tumor cell agent. In this study we investigated whet her curcumin inhibited the response of gamma delta T cells to protease-resi stant phosphorylated derivatives found in the cell wall of many pathogens. The results showed that curcumin levels greater than or equal to 30 muM pro foundly inhibited isopentenyl pyrophosphate-induced release of the chemokin es macrophage inflammatory protein-1 alpha and -1 beta and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-kappaB and AP-1. Commencing around 16 h, treatment with curcumin lead to the inductio n of cell death that could not be reversed by APC, IL-15, or IL-2. This cyt otoxicity was associated with increased annexin V reactivity, nuclear expre ssion of active caspase-3, cleavage of poly(ADP-ribose) polymerase, translo cation of apoptosis-inducing factor to the nucleus, and morphological evide nce of nuclear disintegration. However, curcumin led to only large scale DN A chromatolysis, as determined by a combination of TUNEL staining and pulse -field and agarose gel electrophoresis, suggesting a predominantly apoptosi s-inducing factor-mediated cell death process. We conclude that gamma delta T cells activated by these ubiquitous Ags are highly sensitive to curcumin , and that this effect may contribute to the anti-inflammatory properties o f this compound.