Gieske Mary C, Na Gi Youn, Koo Yongbum, Jo Misung, Curry Thomas E, Ko Chemyong
Department of Clinical Sciences and Biological Sciences, University of Kentucky, Lexington, Kentucky 40506, USA.
J Endocrinol. 2005 Aug;186(2):303-13. doi: 10.1677/joe.1.06218.
One of the most prominent inflammatory reactions is the activation of the complement system. The activated complement system does not distinguish between pathogens and the host cell. In order to prevent autologous complement-mediated attack, host cells express a variety of both membrane-bound and fluid-phase complement regulatory proteins which control activity of the complement cascade by acting on convertase enzymes or the membrane-attack complex. Although the process of ovulation is facilitated by the inflammatory reaction, this reaction has the potential to cause serious damage to growing follicles, ovulated follicles, and other important ovarian tissues. This study was undertaken to characterize the expression and regulation of decay-accelerating factor (DAF), a complement regulator, as a potential mediator of ovarian tissue protection from ovulatory inflammation. DNA microarray and Northern blot analyses showed that an ovulatory gonadotropin stimulus dramatically yet transiently induced DAF mRNA expression in the immature rat ovary. Northern blot and PCR analyses revealed that of the three known DAF isoforms, glycosylphosphatidylinositol (GPI)-, soluble-, and transmembrane-(TM) DAF, GPI-DAF was the predominant form. In situ hybridization localized GPI-DAF mRNA expression in the theca-interstitial cells of the periovulatory ovary. Neither the anti-progestin RU486 nor the cyclooxygenase inhibitor indomethacin significantly inhibited human chorionic gonadotropin (hCG)-induced GPI-DAF mRNA expression in vivo. In vitro theca cell culture studies indicated that hCG induces GPI-DAF mRNA expression through the protein kinase A pathway. This study suggests that gonadotropin-induced GPI-DAF may be involved in the protection of ovarian tissues from the potential attack by the complement system activated by the inflammatory response associated with ovulation.
最显著的炎症反应之一是补体系统的激活。激活的补体系统无法区分病原体和宿主细胞。为了防止自身补体介导的攻击，宿主细胞表达多种膜结合型和液相补体调节蛋白，这些蛋白通过作用于转化酶或膜攻击复合物来控制补体级联反应的活性。尽管排卵过程由炎症反应促进，但这种反应有可能对生长中的卵泡、排卵后的卵泡及其他重要的卵巢组织造成严重损害。本研究旨在表征衰变加速因子（DAF）（一种补体调节因子）的表达和调控情况，其作为卵巢组织免受排卵性炎症潜在攻击的一种潜在介质。DNA微阵列和Northern印迹分析表明，排卵性促性腺激素刺激可显著但短暂地诱导未成熟大鼠卵巢中DAF mRNA的表达。Northern印迹和PCR分析显示，在三种已知的DAF同工型（糖基磷脂酰肌醇（GPI）-、可溶性-和跨膜-（TM）DAF）中，GPI-DAF是主要形式。原位杂交将GPI-DAF mRNA的表达定位在排卵周围卵巢的卵泡膜间质细胞中。抗孕激素RU486和环氧化酶抑制剂吲哚美辛在体内均未显著抑制人绒毛膜促性腺激素（hCG）诱导的GPI-DAF mRNA表达。体外卵泡膜细胞培养研究表明，hCG通过蛋白激酶A途径诱导GPI-DAF mRNA表达。本研究提示，促性腺激素诱导的GPI-DAF可能参与保护卵巢组织免受与排卵相关的炎症反应激活的补体系统的潜在攻击。
