Dipyridamole inhibits lipopolysaccharide-induced cyclooxygenase-2 and monocyte chemoattractant protein-1 via heme oxygenase-1-mediated reactive oxygen species reduction in rat mesangial cells
Dipyridamole inhibits lipopolysaccharide-induced cyclooxygenase-2 and monocyte chemoattractant protein-1 via heme oxygenase-1-mediated reactive oxygen species reduction in rat mesangial cells
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DOI：
10.1016/j.ejphar.2010.09.058
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发表时间：
2011-01-10
影响因子：
5
通讯作者：
Chen, Tso-Hsiao
中科院分区：
文献类型：
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作者：
Chen, Yen-Cheng;Chen, Cheng-Hsien;Chen, Tso-Hsiao
双嘧达莫对多种细胞的炎症反应具有有益作用，其对肾小球系膜细胞的抗炎机制尚不清楚。本研究观察了双嘧达莫对肾小球系膜细胞环氧化酶2（考克斯2）和单核细胞趋化蛋白1（MCP-1）表达水平的影响。在用脂多糖刺激的大鼠肾小球系膜细胞中，发现双嘧达莫抑制脂多糖诱导的考克斯-2和MCP-1。1的表达和脂多糖诱导的活性氧的产生在大鼠系膜细胞中双嘧达莫的这种抑制作用不依赖于环AMP和环GMP增加锡原卟啉IX（SnPP）。本研究通过在大鼠系膜细胞中应用特异性抑制剂，证明ERK 1/2和1338 MAPK信号通路参与脂多糖诱导的肾小球系膜细胞考克斯-2和MCP-1表达，并通过阻断脂多糖诱导的肾小球系膜细胞MCP-1和COX-2的表达，证实了脂多糖诱导的肾小球系膜细胞MCP-1和COX-2的表达。诱导炎症反应，并被SnPP和N乙酰半胱氨酸抑制。此外，还发现潘生丁上调大鼠系膜细胞HO 1。因此，我们的数据表明，潘生丁通过HO-1介导的活性氧减少抑制脂多糖处理的大鼠系膜细胞中考克斯-2和MCP 1的表达ID（C）2010 Elsevier BV All rights reserved
Dipyridamole contributes to its beneficial effects on inflammatory responses in many cell types The anti inflammatory mechanisms of dipyridamole on glomerular mesangial cells are mostly uncharacterized In this study we monitored the influence of dipyridamole on the expression levels of cyclooxygenase 2 (COX 2) and monocyte chemoattractant protein-1 (MCP-1) in rat mesangial cells stimulated with lipopolysaccharide Dipyridamole was found to inhibit lipopolysaccharide-induced COX-2 and MCP-1 expression and reduced lipopolysaccharide induced reactive oxygen species generation In rat mesangial cells This inhibitory effect of dipyridamole is independent on cyclic AMP and cyclic GMP increase Tin protopoiphyrin IX (SnPP) a tu me oxygenase-1(HO-1) inhibitor blocked the inhibitory effect of dipyridamole on lipopolysaccharide-induced COX-2 and MCP-1 expression By applying specific inhibitors in rat mesangial cells ERK1/2 and 1338 MAPK signaling pathways were demonstrated to be involved in the lipopolysaccharide-induced inflammatory responses and were inhibited by SnPP and N acetylcysteine treatment Additionally dipyridamole was also found to upregulate HO 1 in rat mesangial cells Therefore our data suggest that dipyridamole inhibits the expression of COX-2 and MCP 1 in lipopolysaccharide-treated rat mesangial cells via HO-1-mediated reactive oxygen species reduction ID (C) 2010 Elsevier BV All rights reserved