College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
Arch Pharm Res. 2012 Nov;35(11):1961-8. doi: 10.1007/s12272-012-1113-8. Epub 2012 Dec 4.
Artemisinin can be isolated from Artemisia annua L. In addition to its well-known anti-malarial activity, artemisinin has antitumor and anti-microbial effects. In this study, we investigated the effect of artemisinin on the production of IL-12p40, which is important in the generation of T helper 1 responses. Artemisinin significantly induced IL-12p40 production in LPS-stimulated RAW264.7 macrophage cells. To elucidate the signaling molecules regulated by artemisinin in induced IL-12p40 production, the DNA-binding activity of several transcription factors and activation of mitogen-activated protein kinase (MAPK)s were investigated. The band intensities of NF-κB, AP-1, and SP1, and the activation of p38 MAPK and ERK were not changed by artemisinin. However, the induced phosphorylation of JNK was significantly decreased by artemisinin, and inhibition of the JNK signaling pathway further increased IL-12p40 production in LPS-stimulated RAW264.7 macrophage cells. Taken together, these data suggest that artemisinin induces the production of IL-12p40 in LPS-stimulated macrophage cells by inhibiting JNK activity.
青蒿素可以从青蒿中分离得到。除了众所周知的抗疟作用外，青蒿素还具有抗肿瘤和抗微生物的作用。在这项研究中，我们研究了青蒿素对白细胞介素-12p40 产生的影响，白细胞介素-12p40 在产生 T 辅助 1 反应中很重要。青蒿素显著诱导 LPS 刺激的 RAW264.7 巨噬细胞中 IL-12p40 的产生。为了阐明青蒿素在诱导 IL-12p40 产生中调节的信号分子，研究了几种转录因子的 DNA 结合活性和丝裂原活化蛋白激酶（MAPK）的激活。NF-κB、AP-1 和 SP1 的带强度以及 p38 MAPK 和 ERK 的激活均未受青蒿素影响。然而，青蒿素显著降低了 JNK 的诱导磷酸化，而 JNK 信号通路的抑制进一步增加了 LPS 刺激的 RAW264.7 巨噬细胞中 IL-12p40 的产生。综上所述，这些数据表明，青蒿素通过抑制 JNK 活性诱导 LPS 刺激的巨噬细胞中 IL-12p40 的产生。
