Hsu Hsien-Yeh, Chu Li-Chieh, Hua Kuo-Feng, Chao Louis Kuoping
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
J Cell Physiol. 2008 Jun;215(3):603-12. doi: 10.1002/jcp.21206.
Curcumin, a polyphenolic compound derived from plant, regulates heme oxygenase (HO-1) expression within certain cell types; however, the Curcumin-mediated signal transduction in the regulation of HO-1 expression within human monocytes/macrophages is unclear. Herein, we show that Curcumin dose dependently induced HO-1 expression and HO-1 activity through the activation of PKCalpha, PKCdelta/ERK1/2, p38alpha, and PI3-kinase. In addition, H2O2 release is essential for Curcumin-mediated ERK1/2 and p38 phosphorylation and HO-1 expression. Further, Curcumin inhibited LPS-induced IL-1 and IL-6 secretion and blockage of HO-1 expression/activity by HO-1 siRNA or HO-1 inhibitor, SnPP reversed the inhibitory effects of Curcumin on cytokines secretion. HO-1 over-expression produced the same inhibitory effects of Curcumin on IL-1 secretion. Collectively, our results suggest that Curcumin inhibits cytokines secretion within LPS-stimulated monocytes through a mechanism that involves the action of HO-1.
姜黄素是一种从植物中提取的多酚类化合物,可调节某些细胞类型中的血红素加氧酶(HO-1)表达;然而,姜黄素在人单核细胞/巨噬细胞中调节HO-1表达的信号转导尚不清楚。在此,我们表明姜黄素通过激活PKCalpha、PKCdelta/ERK1/2、p38alpha和PI3激酶,剂量依赖性地诱导HO-1表达和HO-1活性。此外,H2O2释放对于姜黄素介导的ERK1/2和p38磷酸化以及HO-1表达至关重要。此外,姜黄素抑制LPS诱导的IL-1和IL-6分泌,HO-1 siRNA或HO-1抑制剂SnPP阻断HO-1表达/活性可逆转姜黄素对细胞因子分泌的抑制作用。HO-1过表达产生了与姜黄素对IL-1分泌相同的抑制作用。总体而言,我们的结果表明,姜黄素通过一种涉及HO-1作用的机制抑制LPS刺激的单核细胞中的细胞因子分泌。