Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-κB signaling

Cucurbitacin E (CucE), a triterpenoid isolated from Cucurbitaceae plants, has been shown to possess an anti-inflammatory or innmunosuppressive activity in vitro and in vivo, yet the underlying mechanism has been incompletely understood. The aim of the present study was to explore its effect on cytokine expression and the underlying mechanism in human Jurkat T cells as a cellular model. The results showed that CucE significantly inhibited the production of interleukin-2, tumor necrosis factor-alpha, and interferon-gamma in culture medium of cells treated with phorbol 12,13-dibutyrate (PDB) plus ionomycin (Ion). Furthermore, the mRNA levels of these cytokines in activated Jurkat T cells were also decreased upon CucE treatment, suggesting a potential modulatory effect on the critical signaling pathways for cytokine expression, including nuclear factor-kappa B (NF-kappa B) or mitogen-activated protein kinases (MAPKs). In support of its effect on the NF-kappa B signaling pathway, CucE decreased the phosphorylation levels of inhibitor of kappa B (I kappa B) and NF-kappa B/p65 in PDB + Ion-stimulated cells. Further supporting this, the nuclear translocation of NF-kappa B/p65 was significantly suppressed in response to PDB plus Ion stimulation in the presence of CucE. The phosphorylation of p38MAPK, c-Jun N-terminal kinase (JNK), and Erk1/2, however, was not decreased or slightly increased at some time points by CucE treatment. Collectively, these data suggest that CucE may exhibit immunosuppressive effect by attenuating critical cytokine expression through down-regulating the NF-kappa B signaling pathway.