| Project/Area Number |
16390020
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
SUGIMOTO Yukihiko Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (80243038)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Satoshi Mukogawa Womens University, Department of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40303846)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 2004: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | prostaglandins / prostanoids / gene expression regulation / allergic asthma / granulocyte-colony stimulating factor / neutrophils / lueal cell / chemokine / 終末糖化産物受容体 / 性ステロイドホルモン / 受精 / 卵丘細胞 / サイトカイン |
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| Research Abstract |
(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.
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