Decoté-Ricardo D, Chagas K K F, Rocha J D B, Redner P, Lopes U G, Cambier J C, Barros de Arruda L, Peçanha L M T
Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, CCS, Bloco I, sala I2-062, Ilha do Fundão, 21944-570 Rio de Janeiro, RJ, Brazil.
Phytomedicine. 2009 Oct;16(10):982-8. doi: 10.1016/j.phymed.2009.01.004. Epub 2009 Mar 20.
Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (tumeric). It was previously described that curcumin had a potent anti-inflammatory effect and inhibited the proliferation of a variety of tumor cells. In the present study, we investigated the inhibitory effects of curcumin on the response of normal murine splenic B cells. Curcumin inhibited the proliferative response of purified splenic B cells from BALB/c mice stimulated with the Toll-like receptor ligands LPS and CpG oligodeoxynucleotides. LPS-induced IgM secretion was also inhibited by curcumin. The proliferative response induced by either the T-independent type 2 stimuli anti-delta-dextran or anti-IgM antibodies was relatively resistant to the effect of curcumin. We investigated the intracellular signaling events involved in the inhibitory effects of curcumin on murine B cells. Curcumin did not inhibit the increase in calcium levels induced by anti-IgM antibody. Western blotting analysis showed that curcumin inhibited TLR ligands and anti-IgM-induced phosphorylation of ERK, IkappaB and p38. Curcumin also decreased the nuclear levels of NFkappaB. Our results suggested that curcumin is an important inhibitor of signaling pathways activated upon B cell stimulation by TLR ligands. These data indicate that curcumin could be a potent pharmacological inhibitor of B cell activation.
姜黄素是从姜黄根茎中分离出的一种酚类天然产物。先前已有描述称姜黄素具有强大的抗炎作用,并能抑制多种肿瘤细胞的增殖。在本研究中,我们研究了姜黄素对正常小鼠脾脏B细胞反应的抑制作用。姜黄素抑制了用Toll样受体配体LPS和CpG寡脱氧核苷酸刺激的BALB/c小鼠纯化脾脏B细胞的增殖反应。姜黄素还抑制了LPS诱导的IgM分泌。由非T细胞依赖2型刺激物抗δ-葡聚糖或抗IgM抗体诱导的增殖反应对姜黄素的作用相对具有抗性。我们研究了姜黄素对小鼠B细胞抑制作用所涉及的细胞内信号转导事件。姜黄素并未抑制抗IgM抗体诱导的钙水平升高。蛋白质免疫印迹分析表明,姜黄素抑制了TLR配体和抗IgM诱导的ERK、IκB和p38的磷酸化。姜黄素还降低了NFκB的核水平。我们的结果表明,姜黄素是TLR配体刺激B细胞时激活的信号通路的重要抑制剂。这些数据表明,姜黄素可能是一种有效的B细胞活化药理学抑制剂。