Gene regulation of interleukin-1β, interleukin-1 receptor type I, and plasminogen activator inhibitor-1 and -2 in human granulosa-luteal cells

To investigate the regulation of messenger ribonucleic acid (mRNA) levels of interleukin-1 beta (IL-1β), interleukin-1 (IL-1) receptor type 1, and plasminogen activator (PA) inhibitor-1 and -2 in cumulus cells, granulosa-luteal cells, and macrophage-depleted granulosa-luteal cells obtained from human preovulatory follicles. Prospective longitudinal study. Patients undergoing assisted reproductive technologies (ART) in the Department of Gynecology and Obstetrics, Stanford University, Stanford, California. Cumulus cells and granulosa-luteal cells were collected by ultrasound-guided transvaginal aspiration at the time of ART. Northern blot analysis of mRNA levels of IL-1β, IL-1 receptor type 1, PA inhibitor-1 and -2 in cumulus cells, granulosa-luteal cells and macrophage-depleted granulosa-luteal cells, and indirect immunocytochemical analysis of the IL-1 system and macrophages in granulosa-luteal cell preparations were performed. Interleukin-1β mRNA levels in uncultured cumulus cells were less than those of uncultured granulosa-luteal cells with no differences in IL-1 receptor type 1 mRNA levels between these two cell types. Granulosa-luteal cell IL-1 receptor type 1 mRNA levels were expressed constitutively throughout 24hours of culture with no effect by hCG, whereas IL-1β mRNA levels increased within 6hours, and then remained elevated for 24hours with no effect by hCG. Interleukin-1β significantly increased granulosa-luteal cell mRNA levels of IL-1β (over twofold), IL-1 receptor type 1 (over twofold), PA inhibitor-1 (approximately 1.4-fold), and PA inhibitor-2 (approximately 1.6-fold). In contrast, IL-1β had no effect on IL-1β and IL-1 receptor type 1 mRNA levels in macrophage-depleted granulosa-luteal cells. Granulosa-luteal cells, not macrophages, account for the majority of the immunocytochemical staining for IL-1β and IL-1 receptor type 1 in follicular aspirates. These studies suggest that the IL-1 system is regulated in human granulosa-luteal cells during the periovulatory period. Furthermore, the augmentation of PA inhibitor-1 and -2 mRNA levels by IL-1β suggests a potential role for IL-1β in remodeling of the human ovary during the periovulatory period.