Cyclooxygenase-2-dependent Prostaglandin E2 Down-regulates Intercellular Adhesion Molecule-1 Expression via EP2/EP4 Receptors in Interleukin-1ß-stimulated Human Gingival Fibroblasts
Cyclooxygenase-2-dependent Prostaglandin E2 Down-regulates Intercellular Adhesion Molecule-1 Expression via EP2/EP4 Receptors in Interleukin-1ß-stimulated Human Gingival Fibroblasts
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环氧合酶 2 依赖性前列腺素 E2 通过 EP2/EP4 受体下调白细胞介素 1ß 刺激的人牙龈成纤维细胞中细胞间粘附分子 1 的表达
DOI：
--
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
I. Ishikawa
中科院分区：
文献类型：
--
作者：
K. Noguchi;K. Iwasaki;M. Shitashige;H. Endo;H. Kondo;I. Ishikawa
前列腺素E2（PGE 2）通过EP受体（EP 1、EP 2、EP 3和EP 4）发挥其作用，是由环氧合酶（考克斯）-1和/或考克斯-2产生的花生四烯酸的生物活性代谢物。我们先前已经证明，PGE下调白细胞介素-1 β（IL-1β）刺激的人牙龈成纤维细胞（HGF）中细胞间粘附分子-1（ICAM-1）的表达。本研究探讨了IL-1β刺激的HGF细胞中PGE 2下调ICAM-1表达的机制中哪一个参与了考克斯的调节，以及哪一种EP受体亚型调节ICAM-1的表达。特异性考克斯-2抑制剂NS-398和考克斯-1/考克斯-2抑制剂吲哚美辛均可完全抑制IL-1β刺激的HGF产生PGE 2。北方杂交和免疫细胞化学染色结果显示，IL-1β刺激的HGF细胞表达考克斯-2的mRNA和蛋白，而未刺激的HGF细胞不表达，且考克斯-1的mRNA和蛋白在未刺激和刺激的HGF细胞中的表达相似。NS-398和吲哚美辛增强IL-1β刺激的HGF细胞ICAM-1表达。根据逆转录/聚合酶链反应，EP 1、EP 2和EP 4受体mRNA在HGF中表达。PGE 2、11-脱氧-PGE 1（一种选择性EP 2/EP 4激动剂）和布他前列素（一种选择性EP 2激动剂）减弱IL-1β诱导的ICAM-1表达，尽管布他前列素的效力低于PGE 2和11-脱氧-PGE 1。AH-23848 B可拮抗PGE 2对IL-1β诱导的ICAM-1表达的抑制作用。EP 1/EP 3激动剂Sulprostone对IL-1β诱导的ICAM-1表达无影响。这些数据的分析表明，考克斯-2衍生的PGE 2通过EP 2/EP 4受体下调IL-1β刺激的HGF中ICAM-1的表达。
Prostaglandin E2 (PGE2), which exerts its actions via EP receptors (EP,, EP2, EP 3, and EP4), is a bioactive metabolite of arachidonic acid produced by cyclooxygenase (COX)-l and/or COX-2. We have previously demonstrated that PGE, downregulates intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1β (IL-1β)-stimulated human gingival fibroblasts (HGF). In the present study, we investigated which COX was involved in down-regulation of ICAM-1 expression by PGE2 in IL-1β-stimulated HGF and which subtypes of EP receptors modulated the ICAM-1 expression. NS-398, a specific COX-2 inhibitor, completely inhibited PGE2 production by IL-1β-stimulated HGF, as did indomethacin, a COX-1/COX-2 inhibitor. Northern blot analysis and immunocytochemical staining showed that mRNA and protein of COX-2 were expressed in IL-1β-challenged HGF, but not in unstimulated HGF, and that the expression of mRNA and protein of COX-1 was similar both in unstimulated and in stimulated cells. NS-398 and indomethacin enhanced ICAM-1 expression in IL-1β-challenged HGF. EP1, EP 2, and EP4 receptor mRNA was expressed in HGF according to reverse-transcription/polymerase chain-reaction. PGE2, 11-deoxy-PGE 1 (a selective EP2/EP4 agonist), and Butaprost (a selective EP2 agonist) attenuated IL-1β-elicited ICAM-1 expression, although Butaprost was less potent than PGE2 and 11-deoxy-PGE1. AH-23848B, an EP4 antagonist, antagonized the inhibitory effect of IL-1β-elicited ICAM-1 expression by PGE2. Sulprostone, an EP1/EP3 agonist, had no effect on IL-1β-elicited ICAM-1 expression. Analysis of these data suggests that COX-2-derived PGE 2 downregulates ICAM-1 expression via EP2/EP 4 receptors in IL-1β-stimulated HGF.
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DOI：
10.1006/bbrc.1993.2470
发表时间：
1993-11-30
影响因子：
3.1
作者：
AN, SZ;YANG, JH;GOETZL, EJ
通讯作者：
GOETZL, EJ
DOI：
10.1016/s0021-9258(18)35698-9
发表时间：
1992-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Soo-Hee Lee;E. Soyoola;P. Chanmugam;Suzanne B. Hart;Wenqin Sun;Hua Zhong;Shuenn S. Liou;D. Simmons;D. Hwang
通讯作者：
Soo-Hee Lee;E. Soyoola;P. Chanmugam;Suzanne B. Hart;Wenqin Sun;Hua Zhong;Shuenn S. Liou;D. Simmons;D. Hwang
影响因子：
3.5
作者：
PAGE, RC
通讯作者：
PAGE, RC
影响因子：
3.1
作者：
S. An;J. Yang;M. Xia;E. Goetzl
通讯作者：
S. An;J. Yang;M. Xia;E. Goetzl
影响因子：
3.5
作者：
OFFENBACHER, S;ODLE, BM;VANDYKE, TE
通讯作者：
VANDYKE, TE