Dalesconols B inhibits lipopolysaccharide induced inflammation and suppresses NF-κB and p38/JNK activation in microglial cells
Dalesconols B inhibits lipopolysaccharide induced inflammation and suppresses NF-κB and p38/JNK activation in microglial cells
复制标题
Dalesconols B 抑制脂多糖诱导的炎症并抑制小胶质细胞中 NF-kappa B 和 p38/JNK 的激活
DOI：
10.1016/j.neuint.2013.03.003
复制
发表时间：
2013-06-01
影响因子：
4.2
通讯作者：
Xu, Yun
中科院分区：
文献类型：
--
作者：
Han, Lijuan;Yin, Kailin;Xu, Yun
旨在抑制小胶质细胞活化的治疗策略可能会导致大多数神经退行性疾病治疗的重大进展。Dalesconols B，也称为TL 2，是一种新发现的来自螳螂相关真菌的聚酮化合物，据报道具有有效的免疫抑制作用。在本研究中，TL 2的抗炎作用在脂多糖（LPS）处理的BV 2小胶质细胞和原代小胶质细胞中进行了研究。我们的观察表明，TL 2预处理显著抑制了LPS刺激的BV 2小胶质细胞中NO和PGE 2的产生，并抑制了促炎介质如诱导型一氧化氮合酶（iNOS）、考克斯-2、TNE-α、IL-1 β、IL-6、MCP-1 α和MIP-1 β的表达。TL 2还可抑制LPS处理的BV 2小胶质细胞NF-κ B核转位以及Akt、p38和JNK MAP激酶通路的磷酸化水平。此外，TL 2还降低BV 2小胶质细胞中A β诱导的TNF-α、IL-1 β和IL-6的产生。此外，TL 2保护原代皮层神经元免受小胶质细胞介导的神经毒性。总之，我们的研究结果表明，TL 2可能是一种有前途的治疗剂，用于减轻与小胶质细胞活化相关的神经退行性疾病的进展。(C)2013爱思唯尔有限公司保留所有权利。
Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. Dalesconols B, also termed as TL2, is a newly found polyketide from a mantis-associated fungus and has been reported to exert potent immunosuppressive effects. In the present study, the anti-inflammatory effects of TL2 was investigated in lipopolysaccharide (LPS)-treated BV2 microglia and primary microglia cells. Our observations indicated that pretreatment with TL2 significantly inhibited the production of NO and PGE2 and suppressed the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), COX-2, TNE-alpha, IL-1 beta, IL-6, MCP-1 alpha and MIP-lot in LPS-stimulated BV2 microglia. The nuclear translocation of NF-kappa B and the phosphorylation level of Akt, p38 and JNK MAP kinase pathways were also inhibited by TL2 in LPS-treated BV2 microglia. Moreover, TL2 also decreased A beta-induced production of TNF-alpha, IL-1 beta and IL-6 in BV2 microglia. Additionally, TL2 protected primary cortical neurons against microglia-mediated neurotoxicity. Overall, our findings suggested that TL2 might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation. (C) 2013 Elsevier Ltd. All rights reserved.