Department of Microbiology, Brain Korea 21 Project for Medical Science, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-752, Korea.
Immune Netw. 2011 Dec;11(6):420-3. doi: 10.4110/in.2011.11.6.420. Epub 2011 Dec 31.
Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-κB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-κB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-κB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.
由于 CKD-712 已被开发为一种抗炎剂，我们研究了 CKD-712 在 TLR4 信号转导过程中的作用。使用表达 TLR4 的 HEK293 细胞，在 LPS 刺激前 1 小时用 CKD-712 进行预处理。通过启动子测定评估 NF-κB 的激活。通过 Western blot 测定 ERK、JNK、p38、IRF3 和 Akt 的激活。CKD-712 抑制了 LPS 触发的 NF-κB 信号转导。CKD-712 并未抑制 ERK、JNK、p38 或 IRF3 的激活，相反，这些分子的激活略有增强。用 LPS 刺激时，Akt 的激活也随着 CKD-712 的预处理而增强，在更高浓度时被抑制。我们认为，在 TLR4 信号转导过程中，CKD-712 抑制 NF-κB 的激活。然而，CKD-712 增强了 Akt 以及 MAP 激酶的激活。因此，我们认为 CKD-712 可能作为一种免疫调节剂发挥作用。
