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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

基本信息

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

项目摘要

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.

为探讨两种环氧合酶（考克斯）在蜕膜PG生成中的作用，采用体外培养的蜕膜基质细胞，用特异性抗体进行免疫细胞化学研究，结果显示考克斯-2和考克斯-1在治疗性流产6 ~ 8周的蜕膜基质细胞中均有表达。与明显组成型表达的考克斯-1相反，考克斯-2通过在培养基中不存在血清的情况下添加白细胞介素-1（IL-1）来诱导。考克斯-2的基础染色水平显著低于考克斯-1。孕酮或地塞米松的加入减弱了考克斯-2的酶染色和PGE 2的产生，这意味着孕酮可能参与了早孕蜕膜抑制前列腺素合成的机制。此外，考克斯-2的特异性抑制剂NS-398在10 μ M剂量下剂量依赖性地抑制IL-1刺激的蜕膜细胞产生PGE 2，并完全阻断PG的产生<-6>。这些结果表明，在这种体外培养条件下，来自早期妊娠的蜕膜基质细胞产生PG完全依赖于考克斯-2途径，并且似乎考克斯-2途径可能与IL-1刺激的蜕膜细胞产生PG有关。1活性可能受不同机制控制，如花生四烯酸利用率或先前报道的酶抑制蛋白。