Substance P-induced cyclooxygenase-2 expression in human umbilical vein endothelial cells
Substance P-induced cyclooxygenase-2 expression in human umbilical vein endothelial cells
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DOI：
10.1038/sj.bjp.0706660
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发表时间：
2006-03-01
影响因子：
7.3
通讯作者：
Fantozzi, R
中科院分区：
文献类型：
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作者：
Gallicchio, M;Rosa, AC;Fantozzi, R
1 P物质(SP)是一种参与神经源性炎症的神经肽，是NK1、NK2和NK3受体的激动剂。SP诱导多种类型的细胞产生前列腺素(PG)，这些二十烷基类化合物负责许多炎症和血管效应。2.需要环氧合酶(COX)将花生四烯酸转化为前列腺素。研究SP对人脐静脉内皮细胞(HUVEC)COX-2蛋白表达的影响。3在相同实验条件下，SP可上调人脐静脉内皮细胞COX-2蛋白表达，100 nM、20h达高峰，COX-1蛋白表达无明显变化。COX-2的表达与PGI(2)和PGE(2)的释放呈正相关。4地塞米松(DEX)抑制SP介导的COX-2的表达。丝裂原活化蛋白激酶(MAPK)p38和p42/44可被SP激活，而其抑制剂SB202190和PD98059可阻断COX-2的表达。5，5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)苯基-2(5H)-呋喃酮(DFU)是一种实验性的选择性COX-2抑制剂，可阻断SP诱导的PG释放。选择性NK1和NK2激动剂[Sar(9)，Met(O-2)(11)]SP和[β-Ala(8)]NKA(4-10)可上调COX-2蛋白表达和PG生成，而选择性NK3激动剂Senktie(Suc-Asp-Phe-MePhe-Gly-Leu-Met-NH2)则无此作用。NK1选择性拮抗剂L703,606((顺)-2-(二苯甲基)-N-((2-碘苯基)甲基)-1-氮杂双环(2.2.2)辛坦-3-胺)和NK2选择性拮抗剂SR 48,968((S)-N-methyl-N-(4-(4-acetylamino-4-phenylpiperidino)-2-(3，4二氯苯基)丁基苯甲酰胺竞争性拮抗SP诱导的作用。从而显示了SP对内皮细胞的先前未被检测到的作用。
1 Substance P (SP) is a neuropeptide involved in neurogenic inflammation and an agonist for NK1, NK2, and NK3 receptors. SP induces prostaglandin ( PG) production in various cell types, and these eicosanoids are responsible for numerous inflammatory and vascular effects.2 Cyclooxygenase ( COX) are needed to convert arachidonic acid to PGs. The study evaluated the effect of SP on COX expression in human umbilical vein endothelial cells ( HUVEC).3 COX-2 protein expression was upregulated by SP with a peak at 100 nM and at 20 h; in the same experimental conditions COX-1 protein expression was unchanged. A correlation between COX-2 expression and PGI(2) and PGE(2) release was detected.4 Dexamethasone (DEX) inhibited SP-mediated COX-2 expression. Mitogen-activated protein kinases ( MAPK) p38 and p42/44 were activated by SP, whereas SB202190 and PD98059, inhibitors of these kinases, blocked COX-2 expression. 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone (DFU), an experimental selective COX-2 inhibitor, blocked SP-induced PG release.5 By RT-PCR and Western blot analysis, we demonstrated that NK1 and NK2 but not NK3 receptors are present on HUVEC. Selective NK1 and NK2 agonists, namely [Sar(9), Met(O-2)(11)] SP and [beta-Ala(8)] NKA(4 - 10), upregulated COX-2 protein expression and PG production, whereas senktide (Suc - Asp - Phe - MePhe - Gly - Leu - Met - NH2), a selective NK3 agonist, was ineffective in this respect. The NK1 selective antagonist L703,606 ((cis)-2-(diphenylmethyl)-N-((2-iodophenyl)- methyl)-1-azabicyclo( 2.2.2) octan-3-amine) and the NK2 selective antagonist SR 48,968 ((S)-N-methyl-N-(4-(4-acetylamino-4-phenylpiperidino)- 2-( 3,4 dichlorophenyl) butyl) benzamide) competitively antagonised SP-induced effects.6 The study shows HUVEC to possess functional NK1 and NK2 receptors, which mediate the ability of SP to induce expression of COX-2 in HUVEC, thus showing a previously-undetected effect of SP on endothelial cells.