Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Global COE "Cell Fate Regulation Research and Education Unit", Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Biochem Biophys Res Commun. 2010 Aug 6;398(4):647-52. doi: 10.1016/j.bbrc.2010.06.126. Epub 2010 Jul 3.
Toll-like receptor-2 (TLR2) is a pattern recognition receptor that senses many types of bacterial components and activates signaling pathways that induce inflammatory cytokines. A hyperresponsiveness to pathogens caused by increased expression of TLR2 triggers exaggeration of some inflammatory diseases. Here, we showed that curcumin, a well-known anti-inflammatory agent derived from the curry spice turmeric, inhibits TLR2 expression in various TLR2-expressing innate immune cell lines such as monocytic THP-1 cells, neutrophilic-differentiated HL-60 cells. Strong suppression of TLR2 gene expression was specifically observed at concentrations of curcumin in the range 40-100muM. Consistent with decreased expression of TLR2 mRNA, protein expression and ligand-responsiveness of TLR2 were markedly reduced by curcumin treatment. Moreover, curcumin-dependent down-regulation of TLR2 expression and function was also observed in primary peripheral blood monocytes (MC) and polymorphonuclear neutrophils (PMN). Finally, we determined the importance of curcumin-dependent radical generation for the suppressive effect of curcumin on TLR2 expression. Thus, our data demonstrate that curcumin inhibits TLR2 gene expression and function possibly via an oxidative process.
Toll 样受体 2（TLR2）是一种模式识别受体，可识别多种细菌成分，并激活诱导炎症细胞因子的信号通路。TLR2 表达增加导致对病原体的高反应性，引发某些炎症性疾病的加重。在这里，我们表明，姜黄素是一种源自咖喱香料姜黄的知名抗炎剂，可抑制各种 TLR2 表达的固有免疫细胞系（如单核细胞 THP-1 细胞、嗜中性粒细胞分化的 HL-60 细胞）中的 TLR2 表达。在 40-100μM 的姜黄素浓度范围内，特异性观察到 TLR2 基因表达的强烈抑制。与 TLR2mRNA 表达减少一致，姜黄素处理也显著降低了 TLR2 的蛋白表达和配体反应性。此外，姜黄素还可下调原代外周血单核细胞（MC）和多形核粒细胞（PMN）中的 TLR2 表达和功能。最后，我们确定了姜黄素依赖性自由基生成对姜黄素抑制 TLR2 表达的抑制作用的重要性。因此，我们的数据表明，姜黄素可能通过氧化过程抑制 TLR2 基因表达和功能。
