Tanshinone IIA inhibits LPS-induced NF-κB activation in RAW 264.7 cells:: Possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways
Tanshinone IIA inhibits LPS-induced NF-κB activation in RAW 264.7 cells:: Possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways
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DOI：
10.1016/j.ejphar.2006.04.044
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发表时间：
2006-08-07
影响因子：
5
通讯作者：
You, Yong-Ouk
中科院分区：
文献类型：
--
作者：
Jang, Seon;Kim, Hyung Jin;You, Yong-Ouk
核因子-κ B诱导激酶（NIK）-I κ B α激酶（IKK）通路和丝裂原活化蛋白激酶（MAPK）通路激活核因子-κ B（NF-κ B）B（NF-κ B B）在炎症中起重要作用。我们最近发现丹参酮IIA是从丹参中分离的一种二萜类化合物。丹参），减少了用脂多糖（LPS）刺激的RAW 264.7细胞中促炎介质的产生。然而，丹参酮IIA对促炎介质产生的抑制机制知之甚少。为了研究其抑制机制，我们测定了丹参酮IIA对NF-κ B和I κ B α磷酸化激活的抑制作用，还检测了NIK和IKK的磷酸化以及MAPK如p38 MAPK（p38）、细胞外信号调节激酶1/2（ERK 1/2）、和c-Jun N-末端激酶（JNK）。丹参酮IIA剂量依赖性地抑制NF-κ B-DNA复合物、NF-κ B结合活性和I κ B α的磷酸化。丹参酮HA还抑制NF-κ B从胞浆到细胞核的移位。此外，丹参酮IIA以剂量依赖性方式抑制LPS刺激的RAW 264.7细胞中NIK和IKK的磷酸化以及p38、ERK 1/2和JNK的磷酸化。这些结果表明，丹参酮IIA可以抑制LPS诱导的I κ B α降解和NF-κ B激活通过抑制NIK-IKK途径以及MAPK（p38，ERK 1/2和JNK）途径在RAW 264.7细胞和这些特性可能提供一个潜在的机制，解释了抗炎活性的丹参酮IIA。(c)2006 Elsevier B. V.保留所有权利。
Nuclear factor kappa B (NF-kappa B) activation by NF-kappa B-inducing kinase (NIK)-I kappa B alpha kinase (IKK) pathway and mitogen-activated protein kinases (MAPKs) pathway are important in inflammation. We recently found that the tanshinone IIA, a diterpene isolated from Salvia miltiorrhiza (S. miltiorrhiza), reduced the production of pro-inflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). However, little is known about the inhibitory mechanisms of tanshinone IIA on the production of pro-inflammatory mediators. To investigate the inhibitory mechanism, we determined the inhibitory effects of tanshinone IIA on the activation of NF-kappa B and I kappa B alpha phosphorylation, and also examined phosphorylation of NIK and IKK as well as the activation of MAPKs such as p38 MAPK (p38), extracellular signal-regulated kinases 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in RAW 264.7 cells stimulated with LPS. Tanshinone IIA inhibited NF-kappa B-DNA complex, NF-kappa B binding activity, and the phosphorylation Of I kappa B alpha in a dose dependent manner. Tanshinone HA also inhibited the translocation of NF-kappa B from cytosol to nucleus. Moreover, the phosphorylation of NIK and IKK as well as the phosphorylation of p38, ERK1/2, and JNK in the LPS-stimulated RAW 264.7 cells were suppressed by the tanshinone IIA in a dose dependent manner. These results suggest that tanshinone IIA may inhibit LPS-induced I kappa B alpha degradation and NF-kappa B activation via suppression of the NIK-IKK pathway as well as the MAPKs (p38, ERK1/2, and JNK) pathway in RAW 264.7 cells and these properties may provide a potential mechanism that explains the anti-inflammatory activity of tanshitione IIA. (c) 2006 Elsevier B.V. All rights reserved.