Sulforaphane suppresses LPS-induced inflammation in primary rat microglia
Sulforaphane suppresses LPS-induced inflammation in primary rat microglia
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DOI：
10.1007/s00011-009-0116-5
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发表时间：
2010-06-01
影响因子：
6.7
通讯作者：
Wruck, Christoph J.
中科院分区：
文献类型：
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作者：
Brandenburg, Lars-Ove;Kipp, Markus;Wruck, Christoph J.
本研究的目的是探讨萝卜硫素（SF）介导的抑制脂多糖（LPS）炎症反应的信号转导途径。此外，我们还研究了SF和LPS对Nrf 2活性的影响。采用原代大鼠小胶质细胞和小鼠小胶质细胞系BV 2，用LPS和SF处理细胞，用WST法检测细胞活力。实时定量RT-PCR分析细胞因子mRNA水平。在LPS刺激的小胶质细胞中测量一氧化氮（NO）释放。通过蛋白质印迹法测定各种信号转导途径和Nrf 2的诱导。通过双荧光素酶法检测NF-κ B和AP-1的活化，我们发现SF减弱了LPS诱导的小胶质细胞中IL-1 β、IL-6和TNF-α表达的增加。此外，SF以浓度依赖性方式显著降低NO。SF抑制LPS刺激的ERK 1/2和JNK磷酸化，从而抑制LPS诱导的NF-κ B-和激活蛋白-1（AP-1）的活化。此外，SF和LPS一起能够诱导Nrf 2激活。我们表明，SF，也LPS本身，能够激活细胞的防御氧化和亲电应激。我们的结论是SF可能是一个候选代理抗炎治疗的中枢神经系统。
The aim of this study was to investigate the signal transduction pathways involved in sulforaphane (SF) mediated inhibition of the inflammatory response to lipopolysaccharide (LPS). Additionally, we investigated the effects of SF and LPS on the activity of Nrf2.Primary rat microglia and the murine microglia cell line BV2 were used.Cells were treated with LPS with or without SF.Cell viability was measured via WST-assay. Real-time RT-PCR was performed to analyze cytokine mRNA levels. The nitric oxide (NO) release was measured in LPS-stimulated microglia. The induction of various signal transduction pathways and Nrf2 was determined by Western blotting. NF-kappa B and AP-1 activation was measured by dual luciferase assay.We showed that SF attenuates the LPS-induced increase of IL-1 beta, IL-6, and TNF-alpha expression in microglia. In addition, SF significantly decreases the NO in a concentration-dependent manner. SF inhibits LPS-stimulated ERK1/2 and JNK phosphorylation and thereby inhibits the LPS-induced activation of NF-kappa B- and activator protein-1 (AP-1). Moreover, SF and LPS together are able to induce Nrf2 activation.We showed that SF, and also LPS by itself, are able to activate the cell's defence against oxidative and electrophilic stress. We conclude that SF could be a candidate agent for anti-inflammatory treatment of the central nervous system.