Melatonin modulates microsomal PGE synthase 1 and NF-E2-related factor-2-regulated antioxidant enzyme expression in LPS-induced murine peritoneal macrophages
Melatonin modulates microsomal PGE synthase 1 and NF-E2-related factor-2-regulated antioxidant enzyme expression in LPS-induced murine peritoneal macrophages
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DOI：
10.1111/bph.12428
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发表时间：
2014-01-01
影响因子：
7.3
通讯作者：
Sanchez-Hidalgo, M.
中科院分区：
文献类型：
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作者：
Aparicio-Soto, M.;Alarcon-de-la-Lastra, C.;Sanchez-Hidalgo, M.
背景和目的越来越多的证据表明，褪黑激素调节炎症和免疫过程，作为这些反应的激活剂和抑制剂。然而，其抗炎作用的分子机制仍不清楚。实验方法分离小鼠腹腔巨噬细胞，在LPS（5 μ mL ~（-1））存在或不存在的情况下，用褪黑素处理18小时，观察褪黑素对LPS刺激的小鼠腹腔巨噬细胞炎症反应的氧化还原调节作用。使用磺酰罗丹明B测定法测定细胞活力，使用Griess反应测定NO产生。关键结果在不影响细胞活力的情况下，褪黑素（12.5、25、50和100 M）可降低亚硝酸盐、诱导型一氧化氮合酶（iNOS）、考克斯-2和微粒体PGE合酶1（mPGES 1）蛋白水平，以及p38 MAPK磷酸化，并阻止NF-B易位。此外，褪黑激素治疗显着增加NF-E2相关因子2（NRF 2）和血红素加氧酶1（HO 1）蛋白水平在小鼠巨噬细胞暴露于LPS.Conclusions和影响褪黑激素减少促炎介质和增强表达HO 1通过NF-B，p38 MAPK和NRF 2级联信号通路在小鼠巨噬细胞。因此，褪黑激素可能是一个有前途的目标与巨噬细胞过度激活的疾病。
Background and Purpose Increasing evidence demonstrates that melatonin regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses. Nevertheless, the molecular mechanisms of its anti-inflammatory action remain unclear. Here we have characterized the cellular mechanisms underlying the redox modulation of LPS-stimulated inflammatory responses in murine peritoneal macrophages by melatonin to provide insight into its anti-inflammatory effects.Experimental Approach Murine peritoneal macrophages were isolated and treated with melatonin in the presence or absence of LPS (5gmL(-1)) for 18h. Cell viability was determined using sulforhodamine B assay and NO production was measured using the Griess reaction. Pro-inflammatory enzymes and transcription factors were detected by Western blotting.Key Results Without affecting cell viability, melatonin (12.5, 25, 50 and 100M) reduced the level of nitrites, inducible NOS (iNOS), COX-2 and microsomal PGE synthase-1 (mPGES1) protein, and p38 MAPK phosphorylation, and prevented NF-B translocation. Furthermore, melatonin treatment significantly increased NF-E2-related factor 2 (Nrf2) and haem oxygenase 1 (HO1) protein levels in murine macrophages exposed to LPS.Conclusions and Implications Melatonin reduced pro-inflammatory mediators and enhanced the expression of HO1 via NF-B, p38 MAPK and Nrf2 cascade signalling pathways in murine macrophages. Thus, melatonin might be a promising target for diseases associated with overactivation of macrophages.