Mechanisms of prostaglandin E2 release by intact cells expressing cyclooxygenase-2: evidence for a 'two-component' model.
Mechanisms of prostaglandin E2 release by intact cells expressing cyclooxygenase-2: evidence for a 'two-component' model.
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表达环氧合酶 2 的完整细胞释放前列腺素 E2 的机制：“双组分”模型的证据。
DOI：
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发表时间：
1999
影响因子：
3.5
通讯作者：
J. Mitchell
中科院分区：
文献类型：
--
作者：
M. Saunders;M. Belvisi;G. Cirino;P. Barnes;T. Warner;J. Mitchell
已知表达组成型环氧合酶-1的细胞中的前列腺素（PG）释放通过磷脂酶A2释放花生四烯酸，随后通过环氧合酶代谢来调节。然而，在表达环氧合酶-2的细胞中磷脂酶A2对PG释放的相对贡献尚不清楚。我们通过放射免疫测定法测定白细胞介素-1 β诱导表达环氧合酶-2（Western印迹分析）的人细胞（A549）释放PGE 2来解决这个问题。细胞未受刺激或用已知激活磷脂酶A2的试剂（缓激肽、Des-Arg 10-胰激肽或钙离子载体A23187）刺激或用外源花生四烯酸处理。当细胞进行处理，表达环氧合酶-2，15分钟内释放的前列腺素E2的水平是检测不到的，然而，在相同的细胞刺激缓激肽，A23187，或花生四烯酸，大量的前列腺素类产生。使用选择性抑制剂/拮抗剂，我们发现缓激肽的作用是由B2受体激活介导的，前列腺素释放是由于环氧合酶-2，而不是环氧合酶-1，活性。此外，我们表明，释放PGE 2刺激缓激肽，A23187，或花生四烯酸被抑制磷脂酶A2抑制剂花生四烯酸三氟甲基酮。因此，我们已经证明，PGE 2是由两个组件：环氧合酶-2的诱导和供应的底物，可能通过激活磷脂酶A2释放。这在A549细胞中通过细胞因子白细胞介素-1 β和激肽缓激肽之间的明显协同作用来说明。
Prostaglandin (PG) release in cells expressing constitutive cyclooxygenase-1 is known to be regulated by liberation of arachidonic acid by phospholipase A2 followed by metabolism by cyclooxygenase. However, the relative contribution of phospholipase A2 to the release of PGs in cells expressing cyclooxygenase-2 is not clear. We addressed this question by using radioimmunoassay to measure PGE2 release by human cells (A549) induced to express cyclooxygenase-2 (measured by Western blot analysis) by interleukin-1beta. Cells were either unstimulated or stimulated with agents known to activate phospholipase A2 (bradykinin, Des-Arg10-kallidin, or the calcium ionophore A23187) or treated with exogenous arachidonic acid. When cells were treated to express cyclooxygenase-2, the levels of PGE2 released over 15 min were undetectable; however, in the same cells stimulated with bradykinin, A23187, or arachidonic acid, large amounts of prostanoid were produced. Using selective inhibitors/antagonists, we found that the effects of bradykinin were mediated by B2 receptor activation and that prostanoid release was due to cyclooxygenase-2, and not cyclooxygenase-1, activity. In addition, we show that the release of PGE2 stimulated by either bradykinin, A23187, or arachidonic acid was inhibited by the phospholipase A2 inhibitor arachidonate trifluoromethyl ketone. Hence, we have demonstrated that PGE2 is released by two components: induction of cyclooxygenase-2 and supply of substrate, probably via activation of phospholipase A2. This is illustrated in A549 cells by a clear synergy between the cytokine interleukin-1beta and the kinin bradykinin.
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DOI：
--
发表时间：
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期刊：
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影响因子：
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DOI：
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发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
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Bartoli,F;Lin,HK;Ghomashchi,F;Gelb,MH;Jain,MK;Apitz-Castro,R
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DOI：
10.1073/pnas.88.7.2692
发表时间：
1991-04-01
影响因子：
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DOI：
10.1016/s0021-9258(18)35698-9
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1992-12
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影响因子：
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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：
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