Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
Chin J Integr Med. 2012 Jan;18(1):34-9. doi: 10.1007/s11655-011-0858-0. Epub 2011 Oct 12.
To investigate the effects of ursolic acid (UA) on T-cell proliferation and activation, as well as to examine its effect on nuclear factor-κB (NF-κB) signaling pathway in T cells.
T-cells isolated from BALB/c mice were incubated with UA at concentrations ranging from 5-30 μmol/L in the presence of phorbol 12-myristate 13-acetate (PMA) or PMA plus ionomycin. The proliferation of T cells was measured by the MTT assay. The expressions of CD69, CD25, and CD71 on T-cell surface were analyzed using flow cytometry. The level of interleukin-2 (IL-2) in the culture supernatant of activated T cells was quantified by enzyme-linked immunosorbent assay (ELISA). The level of phosphorylated IκB-α (p-IκB-α) in total protein and p65, a subunit of NF-κB, nuclear translocation were measured by Western blot analysis.
UA in a dose-dependent manner significantly decreased the proliferation and inhibited the surface expressions of CD69, CD25, and CD71 in murine T lymphocytes upon in vitro activation (P<0.01). Significant reduction of IL-2 production was found in activated T cells treated with UA (P<0.01). The PMA-induced increase in p-IκB-α protein was inhibited, and nuclear translocation of p65 from the cytoplasm was blocked by UA.
UA is a potent inhibitor for T cell activation and proliferation; these effects are associated with the inhibition of NF-κB signaling pathway.
研究熊果酸(UA)对 T 细胞增殖和活化的影响,并探讨其对 T 细胞核因子-κB(NF-κB)信号通路的影响。
用熊果酸(UA)孵育分离自 BALB/c 小鼠的 T 细胞,浓度范围为 5-30 μmol/L,同时加入佛波醇 12-肉豆蔻酸 13-乙酸酯(PMA)或 PMA 加离子霉素。通过 MTT 法测定 T 细胞的增殖。用流式细胞术分析 T 细胞表面 CD69、CD25 和 CD71 的表达。通过酶联免疫吸附试验(ELISA)定量测定激活 T 细胞培养上清液中白细胞介素-2(IL-2)的水平。通过 Western blot 分析测定总蛋白中磷酸化 IκB-α(p-IκB-α)和 NF-κB 亚单位 p65 的核转位水平。
UA 呈剂量依赖性显著降低了体外激活的小鼠 T 淋巴细胞的增殖,并抑制了其表面 CD69、CD25 和 CD71 的表达(P<0.01)。用 UA 处理的激活 T 细胞中发现 IL-2 产生显著减少(P<0.01)。UA 抑制了 PMA 诱导的 p-IκB-α 蛋白增加,并阻断了 p65 从细胞质向核内的转位。
UA 是 T 细胞激活和增殖的有效抑制剂;这些作用与 NF-κB 信号通路的抑制有关。