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
- 作者：Seon Il Jang ; Hyung Jin Kim ; Young-Jun Kim ; Seung-Il Jeong and Yong-Ouk You
- 关键词：Tanshinone IIA ; Nuclear factor κ ; B ; NF-κ ; B-inducing kinase ; Iκ ; B kinase ; Mitogen-activated protein kinase ; Lipopolysaccharide
- 刊名：European Journal of Pharmacology
- 出版年：2006
- 期刊代码：24_00142999
- 类别：neu
- 出版时间：7 August 2006
- 卷：542
- 期：1-3
- 页码：1-7
- 文件大小：585 K
摘要
Nuclear factor κB (NF-κB) activation by NF-κB-inducing kinase (NIK)–IκBα 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-κB and IκBα 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-κB-DNA complex, NF-κB binding activity, and the phosphorylation of IκBα in a dose dependent manner. Tanshinone IIA also inhibited the translocation of NF-κB 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 IκBα degradation and NF-κB 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 tanshinone IIA.