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 immunosuppressive 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-α, and interferon-γ 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-κB (NF-κB) or mitogen-activated protein kinases (MAPKs). In support of its effect on the NF-κB signaling pathway, CucE decreased the phosphorylation levels of inhibitor of κB (IκB) and NF-κB/p65 in PDB + Ion-stimulated cells. Further supporting this, the nuclear translocation of NF-κB/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-κB signaling pathway.
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China Key Laboratory of Physical and Training Adapted Control System, Guangdong Provincial Institute of Sports Science, Guangzhou 510663, China.
Lixian
L
Wang
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Chenguang
C
Li
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Qiuru
Q
Lin
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Xiaoyu
X
Zhang
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Hao
H
Pan
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Lihui
L
Xu
Department of Fetal Medicine, the First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Zijian
Z
Shi
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China thexh@jnu.edu.cn dongyun1967@aliyun.com.
Dongyun
D
Ouyang
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China thexh@jnu.edu.cn dongyun1967@aliyun.com.
Xianhui
X
He
D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
D016207:Cytokines; D016328:NF-kappa B; D014315:Triterpenes; C102326:cucurbitacin E
cucurbitacin E; interferon-γ; interleukin-2; nuclear factor-κB; tumor necrosis factor-α