Non-steroidal anti-inflammatory drugs (NSAIDs) block the late, prostanoid-dependent/ceramide-independent component of ovarian IL-1 action: implications for the ovulatory process.
Non-steroidal anti-inflammatory drugs (NSAIDs) block the late, prostanoid-dependent/ceramide-independent component of ovarian IL-1 action: implications for the ovulatory process.
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非甾体抗炎药 (NSAID) 阻断卵巢 IL-1 作用的晚期前列腺素依赖性/神经酰胺独立成分：对排卵过程的影响。
DOI：
10.1016/s0303-7207(99)00164-1
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发表时间：
1999
影响因子：
4.1
通讯作者：
Adashi,EY
中科院分区：
文献类型：
--
作者：
Ando,M;Kol,S;Irahara,M;Sirois,J;Adashi,EY
非甾体类抗炎药（NSAID）的疗效和抗排卵特性归因于其抑制前列腺素内过氧化物合酶（PGS）活性的能力。鉴于白细胞介素（IL）-1在炎症（可能是排卵）过程中的可能作用，我们开始评估NSAID的抗排卵特性是否部分归因于抑制卵巢IL-1的作用。在不存在或存在指定试剂的情况下，在无血清条件下培养未成熟大鼠的整个卵巢分散液。培养期结束时，提取总RNA，并通过溶液杂交/核糖核酸酶保护试验探测对应于PGS-1、PGS-2、IL-1β、IL-1受体拮抗剂（IL-1 RA）或I型IL-1受体（IL-1 R）的转录物。吲哚美辛治疗对IL-1β的早期（1 h）反应无显著影响;然而，根据PGS-2转录物、蛋白质和活性评估，其导致对IL-1β的晚期（48 h）反应的完全和高度显著的剂量依赖性阻断。加入PGE 2可增强IL-1β上调PGS-2转录的能力。此外，向吲哚美辛处理的细胞中加入PGE 2几乎逆转了吲哚美辛在PGS-2转录和蛋白水平上抑制IL-1β作用的能力。IL-1对IL-1β、IL-1 R和IL-1 RA转录物的上调同样被吲哚美辛抑制。总之，这些观察结果表明，NSAID的抗排卵特性可能部分是由于阻断卵巢IL-1作用的晚期前列腺素依赖性成分。
The therapeutic efficacy and antiovulatory properties of non-steroidal anti-inflammatory drugs (NSAIDs) is attributed to their ability to suppress prostaglandin endoperoxide synthase (PGS) activity. Given the likely role of interleukin (IL)-1 in the inflammatory (and probably the ovulatory) process, we set out to evaluate whether the antiovulatory property of NSAIDs is attributable, in part, to the inhibition of ovarian IL-1 action. Whole ovarian dispersates from immature rats were cultured under serum-free conditions in the absence or presence of the indicated agents. At the conclusion of the culture period, total RNA was extracted and probed for transcripts corresponding to PGS-1, PGS-2, IL-1β, IL-1 receptor antagonist (IL-1RA) or type I IL-1 receptor (IL-1R) by a solution hybridization/ribonuclease protection assay. Treatment with indomethacin was without significant effect on the early (1 h) response to IL-1β; however, it led to complete and highly significant dose-dependent blockade of the late (48 h) response to IL-1β as assessed in terms of PGS-2 transcripts, proteins and activity. The addition of PGE2to cells augmented the ability of IL-1β to upregulate PGS-2 transcripts. Moreover, the addition of PGE2to indomethacin-treated cells all but reversed the ability of indomethacin to suppress the IL-1β effect at both the PGS-2 transcript and protein levels. The upregulation by IL-1 of IL-1β, IL-1R and IL-1RA transcripts was similarly inhibited by indomethacin. Taken together, these observations suggest that the anti-ovulatory property of NSAIDs may be due, in part, to blockade of the late, prostanoid-dependent component of ovarian IL-1 action.