Expression and control mechanisms of prostaglandin H2 synthase in endometrium and decidua

前列腺素H2合酶在子宫内膜和蜕膜中的表达及调控机制

• 批准号: 05671396
• 负责人: ISHIHARA Osamu
• 金额: $ 1.41万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671396/
• 关键词: Cyclooxygenase; Decidua; Interleukin-1; NS-398; Progesterone; Dexamethasone; NS 398; 脱落膜細胞; PGH_2合成酵素; インターロイキン-1; プロゲステロン; デキサメサゾン; HGF; プロスタグランジン; アラキドン酸; PGH2合成酵素; 着床; 12HETE

In order to clarify the involvement of two types of cyclooxygenase (COX) in decidual PG production, subsequent study was undertaken by using in vitro decidual stromal cells culture system.Immunocytochemical study with specific antibody revealed the presence of COX-2 as well as COX-1 in decidual stromal cells obtained at the time of therapeutic abortion between 6 to 8 weeks. In contrast to COX-1 which was apparently expressed constitutively, COX-2 was induced by the addition of interleukin-1 (IL-1) in the absence of serum in culture medium. The basal staining level of COX-2 was significantly lower than that of COX-1. The addition of dexamethasone of progesterone attenuated the induction of COX-2 in terms of both enzyme staining and PGE2 production, which implied the possible involvement of progesterone in the inhibitory mechanism of prostaglandin synthesis by decidua in early pregnancy. In addition, a specific inhibitor of COX-2, NS-398, dose dependently inhibited the PGE2 production by decidual cells stimulated with IL-1 and completely blocked PG production at the dose of 10^<-6>M.These results suggest that PG production by dedidual stromal cells from early pregnancy wholely depend upon COX-2 pathway in this in vitro culture condition and it seems likely that COX-1 activity may be under control of different mechanism such as arachidonic acid availability or previously reported enzyme inhibitory protein.

为了阐明两种类型的环氧合酶（COX）在蜕膜PG产生中的参与，利用体外蜕膜基质细胞培养系统进行了后续研究。用特异性抗体进行的免疫细胞化学研究揭示了COX-2和COX-的存在。 1 在治疗性流产 6 至 8 周期间获得的蜕膜基质细胞中。与明显组成型表达的COX-1相反，COX-2是在培养基中不存在血清的情况下通过添加白介素-1(IL-1)来诱导的。 COX-2的基础染色水平显着低于COX-1。添加地塞米松或孕酮可减弱酶染色和 PGE2 产生方面 COX-2 的诱导，这表明孕酮可能参与了妊娠早期蜕膜合成前列腺素的抑制机制。此外，COX-2的特异性抑制剂NS-398剂量依赖性地抑制用IL-1刺激的蜕膜细胞产生PGE 2 ，并且在10^-6M的剂量下完全阻断PG的产生。这些结果表明在这种体外培养条件下，妊娠早期脱脂基质细胞产生的 PG 完全依赖于 COX-2 途径，并且 COX-1 活性似乎可能受到不同机制的控制，例如花生四烯酸的可用性或先前报道的酶抑制蛋白。

项目成果

石原 理: "着床とプロスタグランディン" ホルモンフロンティア. 2. 129-133 (1995)

石原修：“植入和前列腺素”激素前沿 2. 129-133 (1995)。

O.Ishihara, K.Matsuoka, K.Kinoshita, M.H.F.Sullivan, M.G.Elder: "Interleukin-1beta stimulated PGE2 production from early first trimester human decidual cells is inhibited by dexamethasone and progesterone." Prostaglandins. 49. 15-26 (1995)

O.Ishihara、K.Matsuoka、K.Kinoshita、M.H.F.Sullivan、M.G.Elder：“地塞米松和黄体酮会抑制早孕期人类蜕膜细胞中白细胞介素 1β 刺激的 PGE2 产生。”

石原 理: "プロゲステロンの妊娠初期脱落膜細胞プロスゲグランディン産生に及ぼす影響" 日本受精着床学会雑誌. 10. 251-253 (1993)

Osamu Ishihara：“黄体酮对妊娠早期蜕膜细胞中孕激素产生的影响”，日本受精与着床学会杂志，10. 251-253 (1993)。

Y.Iino, O.Ishihara, K.Kinoshita: "Synthesis of 12-hydroxyeicosatetraenoic acid by human endometrium and decidua" Prostaglandin Leukotrien Essent.Fatty Acids. 49. 609-613 (1993)

Y.Iino、O.Ishihara、K.Kinoshita：“人子宫内膜和蜕膜合成 12-羟基二十碳四烯酸”前列腺素白三烯精华脂肪酸。

O. Ishihara: "Interleukin-1β sfimulated PGE_2 production from early first trimester humandecidual calls is in hibited by dexameethasone and progesterone" Prostaglandins. 49. 15-26 (1995)

O. Ishihara：“地塞米松和黄体酮会抑制妊娠早期人类蜕膜细胞中白细胞介素 1β 刺激的 PGE_2 产生”，Prostaglandins，49. 15-26 (1995)。