Morin downregulates nitric oxide and prostaglandin E2 production in LPS-stimulated BV2 microglial cells by suppressing NF-κB activity and activating HO-1 induction
Morin downregulates nitric oxide and prostaglandin E2 production in LPS-stimulated BV2 microglial cells by suppressing NF-κB activity and activating HO-1 induction
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DOI：
10.1016/j.etap.2016.04.010
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发表时间：
2016-06-01
影响因子：
4.3
通讯作者：
Kim, Gi-Young
中科院分区：
文献类型：
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作者：
Dilshara, Matharage Gayani;Jayasooriya, Rajapaksha Gedara Prasad Tharanga;Kim, Gi-Young
桑色素具有抗感染性休克和过敏反应的抗炎活性，并防止急性肝损伤。然而，桑色素在神经炎症中作用的生物学机制仍然很大程度上未知。因此，本研究探讨桑色素是否具有减弱脂多糖（LPS）刺激的BV 2小胶质细胞中促炎介质如一氧化氮（NO）和前列腺素E-2（PGE（2））表达的能力。桑色素抑制LPS诱导的促炎介质如NO和PGE（2）的表达，而没有任何细胞毒性作用。此外，LPS诱导的诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）在mRNA和蛋白水平上均被桑色素抑制。桑色素还减弱LPS诱导的核转录因子-κ B（NF-κ B）的DNA结合活性及其启动子活性。NF-κ B特异性抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）可下调LPS诱导的iNOS和COX-2的表达，提示桑色素介导的NF-κ B抑制是抑制iNOS和考克斯-2表达的主要信号通路。此外，桑色素增加血红素加氧酶-1（HO-1）活性的诱导，导致NO和PGE（2）的产生受到抑制。我们的研究结果表明桑色素通过抑制NF-κ B B活性和HO-1的激活，下调了LPS刺激的BV 2小胶质细胞中参与NO和PGE（2）合成的促炎基因如iNOS和考克斯-2的表达。总之，本研究的结果表明，桑色素可能有潜力作为预防神经炎症的治疗。(C)2016爱思唯尔B. V.保留所有权利。
Morin possesses anti-inflammatory activity against septic shock and allergic responses, and prevents acute liver damage. However, the biological mechanism of action of morin in neuroinflammation remains largely unknown. Therefore, the present study investigated whether morin has the ability to attenuate expression of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E-2 (PGE(2)) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Morin inhibited the expression of LPS-induced proinflammatory mediators such as NO and PGE(2), without any cytotoxic effects. Furthermore, LPS-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited both at the mRNA and protein levels in response to morin. Morin also attenuated LPS-induced DNA-binding activity of nuclear transcription factor-kappa B (NF-kappa B) and its promoter activity. Pyrrolidine dithiocarbamate (PDTC), a specific NF-kappa B inhibitor, downregulated the expression of LPS-induced iNOS and COX-2, which suggests that morin-mediated NF-kappa B inhibition is the main signaling pathway responsible for the inhibition of iNOS and COX-2 expression. Additionally, morin increased induction of heme oxygenase-1 (HO-1) activity, leading to the suppression of NO and PGE(2) production. Our results indicate that morin downregulates the expression of proinflammatory genes, such as iNOS and COX-2, involved in the synthesis of NO and PGE(2) in LPS-stimulated BV2 microglial cells by suppressing NF-kappa B activity and activation of HO-1. Taken together, the findings of the present study suggest that morin may have potential as a therapeutic for the prevention of neuroinflammation. (C) 2016 Elsevier B.V. All rights reserved.