Proinflammatory Stimulants Promote the Expression of a Promiscuous G Protein-Coupled Receptor, mFPR2, in Microvascular Endothelial Cells
Proinflammatory Stimulants Promote the Expression of a Promiscuous G Protein-Coupled Receptor, mFPR2, in Microvascular Endothelial Cells
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DOI：
10.1007/s10753-011-9358-9
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发表时间：
2012-04-01
期刊：
影响因子：
5.1
通讯作者：
Le, Yingying
中科院分区：
文献类型：
--
作者：
Mou, Haiwei;Li, Zongmeng;Le, Yingying
人甲酰肽受体2(FPR2)及其小鼠同源基因mFPR2属于G蛋白偶联的七跨膜受体超家族。FPR2和mFPR2都识别与促炎条件相关的各种外源和宿主来源的趋化性多肽。由于内皮细胞积极参与炎症反应，我们研究了微血管内皮细胞是否表达mFPR2，以及促炎症因子对其的调节作用。我们发现静息的原代小鼠微血管内皮细胞和细胞系bEnd.3在mRNA和蛋白水平都表达低水平的mFPR2，而两种关键的促炎刺激剂-脂多糖(LPS)和白介素1β(IL-1β)显著增强了mFPR2的表达。内毒素的诱导作用依赖于JNK的MAPK，而JNK和ERK的MAPK均被IL-1β激活以增强mFPR2的表达。显性负性I-kappaBα的过表达可减弱内毒素和IL-1β诱导的mFPR2表达，提示核因子-kappaB在促炎刺激剂调节内皮细胞mFPR2表达中起重要作用。我们的结果表明，炎症条件下血管内皮细胞mFPR2表达上调可能介导了mFPR2激动剂升高的疾病的细胞反应。
Human formylpeptide receptor 2 (FPR2) and its mouse homologue mFPR2 belong to the G protein-coupled, seven-transmembrane receptor superfamily. Both FPR2 and mFPR2 recognize a variety of exogenous and host-derived chemotactic peptides associated with proinflammatory conditions. Since endothelial cells actively participate in inflammation, we investigated whether microvascular endothelial cells express mFPR2 and its regulation by proinflammatory factors. We found that resting primary mouse microvascular endothelial cells and a cell line bEnd.3 expressed low levels of mFPR2 at both mRNA and protein levels, which was markedly enhanced by two key proinflammatory stimulants, lipopolysaccharide (LPS) and interleukin (IL)-1 beta. While the inductive effect of LPS was dependent on the JNK MAP kinase, both JNK and ERK MAP kinases were utilized by IL-1 beta to enhance mFPR2 expression. Overexpression of dominant-negative I kappa B alpha attenuated LPS- and IL-1 beta-induced mFPR2 expression, indicating an essential role for NF-kappa B in regulating mFPR2 expression in endothelial cells by proinflammatory stimulants. Our results suggest that upregulated mFPR2 in vascular endothelial cells under inflammatory conditions may mediate cell responses in diseases in which mFPR2 agonists are elevated.