c-Kit Ligand Mediates Increased Expression of Cytosolic Phospholipase A, Prostaglandin Endoperoxide Synthase-1, and Hematopoietic Prostaglandin D Synthase and Increased IgE-dependent Prostaglandin D Generation in Immature Mouse Mast Cells (*)
c-Kit Ligand Mediates Increased Expression of Cytosolic Phospholipase A, Prostaglandin Endoperoxide Synthase-1, and Hematopoietic Prostaglandin D Synthase and Increased IgE-dependent Prostaglandin D Generation in Immature Mouse Mast Cells (*)
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c-Kit 配体介导未成熟小鼠肥大细胞中胞浆磷脂酶 A、前列腺素内过氧化物合酶-1 和造血前列腺素 D 合酶的表达增加以及 IgE 依赖性前列腺素 D 生成的增加 (*)
DOI：
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发表时间：
1995
影响因子：
4.8
通讯作者：
J. Arm
中科院分区：
文献类型：
--
作者：
M. Murakami;Ryoji Matsumoto;Y. Urade;K. Austen;J. Arm
我们通过评估内源性花生四烯酸合成 PGD2 所涉及的转录物、翻译蛋白水平和酶活性的变化，研究了小鼠肥大细胞中 IgE 依赖性前列腺素 (PG) D2 生成的细胞因子调节。当用WEHI-3细胞条件培养基作为白细胞介素(IL)-3 (BMMC)来源来培养骨髓细胞而衍生的小鼠肥大细胞在重组c-kit配体(KL)中培养、用IgE致敏并用抗原刺激时，PGD2的产生增加了3倍；当 KL 与 IL-3、IL-9 或 IL-10 组合时，PGD2 的生成量比单独在 IL-3 中培养的细胞的生成量增加 6-8 倍。 BMMC 增加的 IgE 依赖性 PGD2 生成在培养 1 天后很明显，在培养 2-4 天后达到最大值，并且对于 KL 和每种辅助细胞因子呈剂量依赖性。细胞与 KL 一起培养后，IgE 依赖性白三烯 C4 的生成增加了 2 倍，而添加 IL-3、IL-9 或 IL-10 则不会增加。通过 RNA 印迹分析稳态转录物，通过 SDS-PAGE/免疫印迹分析蛋白质，以及通过酶活性分析功能，结果表明，KL 单独刺激胞质磷脂酶 A2 (cPLA2)、前列腺素内过氧化物合酶 (PGHS)-1 和末端酶、造血 PGD2 合酶的表达增加，且没有变化 5-脂氧合酶的表达。 IL-3、IL-9 和 IL-10 各自增强 KL 诱导的 PGHS-1 表达。相比之下，细胞在KL+IL-3中培养5小时后短暂检测到的PGHS-2转录本在随后IgE依赖性PGD2生成增加期间不表达。这些发现表明，KL上调cPLA2、PGHS-1和造血PGD2合酶的表达，导致BMMC中内源释放的花生四烯酸依赖于IgE的PGD2产量相对选择性增加，并且它们提供了造血PGD2合酶的细胞因子调节的第一个例子。
We have examined the cytokine regulation of IgEdependent prostaglandin (PG) D2 generation in mouse mast cells by assessing the changes in the levels of the transcript, translated protein, and activity of the enzymes involved in the synthesis of PGD2 from endogenous arachidonic acid. When mouse mast cells, derived by culture of bone marrow cells with WEHI-3 cell-conditioned medium as a source of interleukin (IL)-3 (BMMC), were cultured in recombinant c-kit ligand (KL), sensitized with IgE, and stimulated with antigen, PGD2 generation increased 3-fold; when KL was combined with IL-3, IL-9, or IL-10, PGD2 generation increased 6-8-fold above that produced by the cells cultured in IL-3 alone. The increased IgE-dependent PGD2 generation by BMMC was apparent after 1 day of culture, reached a maximum after 2-4 days of culture, and was dose-dependent for KL and for each of the accessory cytokines. IgE-dependent generation of leukotriene C4 increased 2-fold after the cells were cultured with KL and was not increased by the addition of IL-3, IL-9, or IL-10. Assays for steady-state transcripts by RNA blotting, for protein by SDS-PAGE/immunoblotting, and for function by enzymatic activities revealed that KL alone stimulated the increased expression of cytosolic phospholipase A2 (cPLA2), prostaglandin endoperoxide synthase (PGHS)-1, and the terminal enzyme, hematopoietic PGD2 synthase, without a change in expression of 5-lipoxygenase. IL-3, IL-9, and IL-10 each enhanced the KL-induced expression of PGHS-1. In contrast, transcripts for PGHS-2, which were detected transiently after the cells had been cultured for 5 h in KL + IL-3, were not expressed during the period of subsequent increase in IgE-dependent PGD2 generation. These findings demonstrate that KL up-regulates expression of cPLA2, PGHS-1, and hematopoietic PGD2 synthase, leading to a relatively selective increase in IgE-dependent production of PGD2 from endogenously released arachidonic acid in BMMC, and they provide the first example of cytokine regulation of hematopoietic PGD2 synthase.
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DOI：
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发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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DOI：
10.1073/pnas.88.7.2692
发表时间：
1991-04-01
影响因子：
11.1
作者：
XIE, WL;CHIPMAN, JG;SIMMONS, DL
通讯作者：
SIMMONS, DL
影响因子：
4.4
作者：
Michele Columbo;E. Horowitz;Luis M. Botana;D. MacGlashan;B. Bochner;S. Gillis;Krisztina M. Zsebo;Stephen J. Galli;LAWRENCEM. Lichtenstein
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Michele Columbo;E. Horowitz;Luis M. Botana;D. MacGlashan;B. Bochner;S. Gillis;Krisztina M. Zsebo;Stephen J. Galli;LAWRENCEM. Lichtenstein