Physiological roles of gene expression regulation of prostaglandin receptors

(1) EP3缺失小鼠发生变应性炎症的程度明显高于野生型小鼠或其他前列腺素E受体缺失小鼠。相反，ep3选择性激动剂抑制炎症。当抗原激发后3小时给予激动剂时，这种抑制是有效的，并且与过敏相关基因表达的抑制有关。因此，PGE_2-EP3通路是过敏反应的重要负调节因子。(2)我们发现PGE_2诱导粒细胞集落刺激因子（G-CSF）从腹膜中性粒细胞释放。EP2激动剂可以模拟PGE_2对G-CSF释放的影响，而EP4激动剂则不能。在酪蛋白诱导的腹膜炎中，注射酪蛋白的腹腔中G-CSF的出现与中性粒细胞浸润的时间和渗出液中PGE_2的水平密切相关。ep2缺陷小鼠腹膜渗出液中G-CSF含量显著降低，中性粒细胞迁移和局部PGE_2产生也有类似的反应，表明PGE_2- ep2系统在急性炎症期间参与局部G-CSF的产生。(3)野生型和fp缺陷小鼠妊娠第19天黄体（CL）基因表达谱分析显示，雄激素产生相关酶的表达增加，雌激素合成相关酶的表达减少。我们还发现了6个致力于消除自由基的基因，这些基因在野生型CL中相对于fp缺陷CL被下调。在野生型小鼠妊娠第15 ~ 19天的CL中，类固醇基因和抗氧化基因的表达也发生了类似的变化。因此，雄激素：雌激素生物合成比例的增加，以及自由基清除蛋白表达的显著降低，可能在黄体溶解过程中发挥重要作用。

(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.