Influence of natural and recombinant interleukin 2 on endothelial cell arachidonate metabolism. Induction of de novo synthesis of prostaglandin H synthase.
Influence of natural and recombinant interleukin 2 on endothelial cell arachidonate metabolism. Induction of de novo synthesis of prostaglandin H synthase.
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天然和重组白细胞介素2对内皮细胞花生四烯酸代谢的影响。
DOI：
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发表时间：
1988
影响因子：
15.9
通讯作者：
K. Wu
中科院分区：
文献类型：
--
作者：
K. Frasier;H. Hatzakis;D. Seong;C. M. Jones;K. Wu
我们研究了天然和重组人白介素2(rIL-2)对前列环素(PGI2)、血管内皮生长因子(VWF)和组织型纤溶酶原激活物(TPA)分泌的影响。IL-2可诱导培养的人脐静脉内皮细胞和牛主动脉内皮细胞合成PGI2，但对VWF和tPA无明显影响。纯化的天然IL-2(nIL-2)和rIL-2均能显著促进PGI2的合成。用丝氨酸或丙氨酸取代rIL-2的125位半胱氨酸残基可导致HUVECs中PGI2刺激活性的丧失，而不影响淋巴细胞中胸苷的掺入。高效液相色谱法分析花生四烯酸代谢产物主要检测到6-酮-前列腺素F1α(6KPGF1α)峰。放线菌素D和放线菌素D处理培养的内皮细胞后，6KPGF1α的合成受到抑制。用抗PGH合成酶的多克隆抗体进行的Western印迹显示，pGH合成酶70-kD亚基被nIL-2和rIL-2所增加，但不被丙氨酸取代的rIL-2所增加。我们认为IL-2刺激PGI2持续产生的机制包括PGH合成酶的从头合成。这种调节AA代谢的机制可能具有重要的生理意义。
We studied the effects of natural and recombinant human IL-2 (rIL-2) on secretion of prostacyclin (PGI2), vWf, and tissue-type plasminogen activator (tPA). IL-2 elicited a steady increase in PGI2 synthesis by cultured human umbilical vein endothelial cells (HUVECS) and bovine aortic endothelial cells but had no effect on vWf or tPA. Both purified natural IL-2 (nIL-2) and rIL-2 induced significant PGI2 synthesis. Substitution of the cysteine residue at position 125 of rIL-2 with serine or alanine led to loss of PGI2-stimulatory activity in HUVECS without affecting thymidine incorporation in lymphocytes. HPLC analysis of arachidonate metabolites detected predominantly 6 keto-PGF1 alpha (6KPGF1 alpha) peak. Treatment of cultured endothelial cells with cycloheximide and actinomycin D resulted in inhibition of 6KPGF1 alpha synthesis. The Western blot using a polyclonal antibody against PGH synthase revealed an increment in the 70-kD subunit of PGH synthase by nIL-2 and rIL-2, but not by alanine-substituted rIL-2. We conclude that IL-2 stimulated sustained PGI2 production by a mechanism that includes the de novo synthesis of PGH synthase. This mechanism for regulating AA metabolism probably has important physiologic implications.
DOI：
10.1172/jci112995
发表时间：
1987-06
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
K. Wu;A. Papp;C. Manner;E. Hall
通讯作者：
K. Wu;A. Papp;C. Manner;E. Hall
灌注兔主动脉中花生四烯酸代谢物对血管前列腺素合成的调节。
DOI：
10.1172/jci110993
发表时间：
1983
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Kent,RS;Diedrich,SL;Whorton,AR
通讯作者：
Whorton,AR
人白细胞介素2在特定抗原存在下可促进单个半抗原特异性B细胞的生长和分化。
DOI：
10.1073/pnas.81.24.7917
发表时间：
1984
影响因子：
11.1
作者：
Pike,BL;Raubitschek,A;Nossal,GJ
通讯作者：
Nossal,GJ