Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro
Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro
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DOI：
10.1016/j.bcp.2004.03.015
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发表时间：
2004-07-01
影响因子：
5.8
通讯作者：
Gautam, SC
中科院分区：
文献类型：
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作者：
Gao, XH;Kuo, J;Gautam, SC
姜黄素（二阿魏酰甲烷）是在香料姜黄中发现的主要姜黄素类化合物，具有抗炎、抗氧化和化学预防活性。然而，姜黄素对T细胞介导的免疫反应的发展的影响在很大程度上仍然未知。在这项研究中，我们研究了姜黄素对丝裂原/抗原诱导的脾淋巴细胞增殖，诱导细胞毒性T淋巴细胞（CTL），淋巴因子激活的杀伤（LAK）细胞，以及T淋巴细胞和巨噬细胞产生细胞因子的影响。我们发现，有丝分裂原，白细胞介素-2（IL-2）或同种异体抗原诱导的脾淋巴细胞的增殖，和细胞毒性T淋巴细胞的发展显着抑制在12.5-30 μ mol/L姜黄素。与抗原特异性CTL的产生相比，在相似浓度下LAK细胞的产生对姜黄素的抑制作用不太敏感。姜黄素不可逆地损害了这些免疫功能的产生，因为淋巴细胞未能响应8小时的姜黄素预处理后的激活信号。姜黄素还不可逆地抑制脾T淋巴细胞的IL-2和干扰素-γ（IFN-γ）的表达/产生以及腹腔巨噬细胞的IL-12和肿瘤坏死因子-α（TNF-α）的表达/产生。姜黄素抑制转录因子核因子κ B（NF-κ B）的激活，而不影响组成型表达的NF-κ B的水平。后一结果表明，姜黄素最有可能通过抑制参与诱导这些免疫应答的NF-κ B靶基因来抑制细胞增殖、细胞介导的细胞毒性（CMC）和细胞因子产生。(C)2004年爱思唯尔公司All rights reserved.
Curcumin (diferuloylmethane), a major curcumanoid found in the spice turmeric, exhibits anti-inflammatory, anti-oxidant, and chemopreventive activities. However, the effect of curcumin on the development of T cell-mediated immunological responses largely remains unknown. In this study we have investigated the effect of curcumin on mitogen/antigen induced proliferation of splenic lymphocytes, induction of cytotoxic T lymphocytes (CTLs), lymphokine activated killer (LAK) cells, and the production of cytokines by T lymphocytes and macrophages. We found that mitogen, interleukin-2 (IL-2) or alloantigen induced proliferation of splenic lymphocytes, and development of cytotoxic T lymphocytes is significantly suppressed at 12.5-30 mumol/L curcumin. The generation of LAK cells at similar concentrations was less sensitive to the suppressive effect of curcumin compared to the generation of antigen specific CTLs. Curcumin irreversibly impaired the production of these immune functions, since lymphoid cells failed to respond to the activation signals following 8 h pretreatment with curcumin. Curcumin also inhibited the expression/production of IL-2 and interferon-gamma (IFN-gamma) by splenic T lymphocytes and IL-12 and tumor necrosis factor-alpha (TNF-alpha) by peritoneal macrophages irreversibly. Curcumin inhibited the activation of the transcription factor nuclear factor kappaB (NF-kappaB) without affecting the levels of constitutively expressed NF-kappaB. The latter result suggests that curcumin most likely inhibits cell proliferation, cell-mediated cytotoxicity (CMC), and cytokine production by inhibiting NF-kappaB target genes involved in induction of these immune responses. (C) 2004 Elsevier Inc. All rights reserved.