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Physiological roles of gene expression regulation of prostaglandin receptors

前列腺素受体基因表达调控的生理作用

基本信息

批准号：
16390020
负责人：
SUGIMOTO Yukihiko
金额：
$ 9.47万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

(1)Mice lacking EP3 developed allergic inflammation that was much more pronounced than that in wild-type mice or mice deficient in other prostaglandin (PG) E receptor subtypes. Conversely, an EP3-selective agonist suppressed the inflammation. This suppression was effective when the agonist was administered 3 h after antigen challenge and was associated with inhibition of allergy-related gene expression. Thus, the PGE_2-EP3 pathway is an important negative modulator of allergic reactions. (2)We found that PGE_2 induced granulocyte colony-stimulating factor (G-CSF) release from peritoneal neutrophils. The effect of PGE_2 on G-CSF release was mimicked by an EP2 agonist, but not an EP4 agonist. In the casein-induced peritonitis, the appearance of G-CSF in the casein-injected peritoneal cavity associated well with the timing of neutrophil infiltration as well as PGE_2 levels in exudates. EP2-deficient mice exhibited a strikingly reduced G-CSF content in peritoneal exudates with comparable responses in neutrophil migration and local PGE_2 production, suggesting that the PGE_2-EP2 system contributes to the local production of G-CSF during acute inflammation. (3)Gene expression profile analysis in the corpus luteum (CL) of wild-type and FP-deficient mice on Day 19 of pregnancy revealed an increase in the expression of enzymes involved in androgen production, along with a decrease in the expression of enzymes implicated in estrogen synthesis. We also identified six genes committed to the elimination of free radical species that are down-regulated in the wild-type CL with respect to FP-deficient CL. Similar changes in the expression of steroidogenic and antioxidant genes were found in the CL of wild-type mice between Days 15 and 19 of pregnancy. Thus, an increase in the androgen : estrogen biosynthesis ratio, along with a significantly reduced expression of free radical scavenger proteins, may play an important role in the luteolytic process.

（1）缺乏EP 3的小鼠发生过敏性炎症，其比野生型小鼠或其他前列腺素（PG）E受体亚型缺乏的小鼠中的过敏性炎症明显得多。相反，EP 3选择性激动剂抑制炎症。这种抑制是有效的，当激动剂给药后3小时抗原的挑战，并与过敏相关的基因表达的抑制。因此，PGE_2-EP 3通路是过敏反应的重要负性调节剂。(2)We发现PGE_2可诱导腹膜中性粒细胞释放粒细胞集落刺激因子（G-CSF）。PGE_2对G-CSF释放的作用可被EP_2激动剂所模拟，但不能被EP_4激动剂所模拟。在酪蛋白诱导的腹膜炎中，注射酪蛋白的腹膜腔中G-CSF的出现与中性粒细胞浸润的时间以及渗出液中PGE_2水平密切相关。EP 2缺陷小鼠腹腔渗出液中G-CSF含量显著降低，而中性粒细胞迁移和局部PGE_2产生的反应与EP 2缺陷小鼠相当，提示急性炎症时PGE_2-EP 2系统参与局部G-CSF的产生。（3）在妊娠第19天，野生型和FP缺陷小鼠的黄体（CL）中的基因表达谱分析显示，与雄激素产生有关的酶的表达增加，沿着与雌激素合成有关的酶的表达减少。我们还确定了6个基因致力于消除自由基的物种是下调野生型CL相对于FP缺陷型CL。在妊娠第15天和第19天之间，在野生型小鼠的CL中发现了类固醇生成和抗氧化基因表达的类似变化。因此，雄激素：雌激素生物合成比例的增加，沿着自由基清除蛋白表达的显著降低，可能在黄体溶解过程中起重要作用。

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A cluster of aromatic amino acids in the i2 loop plays a key role for Gs coupling in prostaglandin EP2 &EP3 receptors.

i2 环中的一簇芳香族氨基酸在前列腺素 EP2 中的 Gs 偶联中发挥关键作用

DOI：
发表时间：
2004
期刊：
J. Biol. Chem 279
影响因子：
0
作者：
Sugimoto;Y.;et al.
通讯作者：
et al.

Ca2+ influx‐mediated histamine synthesis and IL‐6 release in mast cells activated by monomeric IgE

DOI：
10.1002/eji.200425622
发表时间：
2005-02
期刊：
European Journal of Immunology
影响因子：
5.4
作者：
Satoshi Tanaka;Sonoko Mikura;Eri Hashimoto;Y. Sugimoto;A. Ichikawa
通讯作者：
Satoshi Tanaka;Sonoko Mikura;Eri Hashimoto;Y. Sugimoto;A. Ichikawa

Critical role of protein kinase C beta II in activation of mast cells by monomeric IgE.

蛋白激酶 C beta II 在单体 IgE 激活肥大细胞中的关键作用。

DOI：
发表时间：
2005
期刊：
J.Biol.Chem. 280
影响因子：
0
作者：
Liu Y;Furuta K;Teshima R;Shirata N;Sugimoto Y;Ichikawa A;Tanaka S.
通讯作者：
Tanaka S.

Microarray evaluation of EP4 receptor-mediated prostaglandin E2 suppression of 3T3-L1 adipocyte differentiation.

DOI：
10.1016/j.bbrc.2004.07.194
发表时间：
2004-09
期刊：
Biochemical and biophysical research communications
影响因子：
3.1
作者：
Y. Sugimoto;Hiroaki Tsuboi;Y. Okuno;Shigero Tamba;Soken Tsuchiya;G. Tsujimoto;A. Ichikawa
通讯作者：
Y. Sugimoto;Hiroaki Tsuboi;Y. Okuno;Shigero Tamba;Soken Tsuchiya;G. Tsujimoto;A. Ichikawa

Suppression of allergic inflammation by prostaglandin E receptor subtype EP3.

前列腺素 E 受体亚型 EP3 抑制过敏性炎症。