Xu Y X, Pindolia K R, Janakiraman N, Chapman R A, Gautam S C
Division of Hematology/Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.
Hematopathol Mol Hematol. 1997;11(1):49-62.
We have previously demonstrated that anti-inflammatory and antioxidant compound curcumin (diferuloyl-methane) inhibits the expression of monocyte chemoattractant protein-1 (MCP-1/JE) in bone marrow stromal cells by suppressing the transcriptional activity of the MCP-1/JE gene. Since both AP-1 (TRE) and NF-kB (kB) binding motifs are present in the promoter of MCP-1/JE gene, we examined the effect of curcumin on IL1 alpha- and TNF-alpha-induced activation of ubiquitous transcription factors AP-1 and NF-kB by electrophoretic mobility shift assay and Western blotting. IL1 alpha and TNF-alpha rapidly induced both AP-1 and NF-kB DNA binding activities in +/+(-)1.LDA11 stromal cells. However, treatment of these cells with curcumin blocked the activation of AP-1 and NF-kB by both cytokines. These data suggest that inhibition of MCP-1/JE transcription by curcumin involves blocking of AP-1 and NF-kB activation by IL1 alpha or TNF-alpha.
我们之前已经证明，抗炎和抗氧化化合物姜黄素（二阿魏酰甲烷）通过抑制单核细胞趋化蛋白-1（MCP-1/JE）基因的转录活性，抑制骨髓基质细胞中单核细胞趋化蛋白-1（MCP-1/JE）的表达。由于MCP-1/JE基因启动子中存在AP-1（TRE）和NF-κB（κB）结合基序，我们通过电泳迁移率变动分析和蛋白质印迹法研究了姜黄素对IL-1α和TNF-α诱导的普遍转录因子AP-1和NF-κB激活的影响。IL-1α和TNF-α在+/+(-)1.LDA11基质细胞中迅速诱导AP-1和NF-κB的DNA结合活性。然而，用姜黄素处理这些细胞可阻断两种细胞因子对AP-1和NF-κB的激活。这些数据表明，姜黄素对MCP-1/JE转录的抑制涉及阻断IL-1α或TNF-α对AP-1和NF-κB的激活。
