IL-1β and PA system in endometriosis

Objective To study the role of Interleukin-1β and plasminogen activating system members in endometriosis migration/invasion. Design Primary cultures of endometriotic stromal cells. Subjects Patients with surgically excised endometriosis. Interventions Interleukin-1β stimulation of primary cultures of endometriotic stromal cells, and knockdown of plasminogen activating system members urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor-1. Main outcome measures Invasion/migration assays Results In primary cultures, Interleukin-1β stimulated endometriotic stromal cell production of the plasminogen activating system members urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor-1. Interleukin-1β also enhanced endometriotic stromal cell migration and invasion, and these effects were inhibited by the Interleukin-1R1 antagonist Anakinra. Knockdown of each of the three plasminogen activating system members also inhibited endometriotic stromal cell migration and invasion. Knockdown of these plasminogen activating system members further attenuated the impact of Interleukin-1β on migration and invasion, suggesting that they mediated the pro-migration and pro-invasion effects of Interleukin-1β. To supplement the cell culture work, immunohistochemistry was carried out on tissue sections of endometriosis epithelium/stroma: urokinase plasminogen activator, plasminogen activator inhibitor-1, and Interleukin-1β H-scores were not found to be correlated with each other. Conclusion In primary cultures of endometriosis stromal cells, Interleukin-1β induces migration and invasion, which is mediated by plasminogen activating system members, and inhibited by the drug Anakinra. However, immunohistochemistry expression of Interleukin-1β, urokinase plasminogen inhibitor-1 and plasminogen activator inhibitor-1 were not correlated, suggesting other regulatory mechanisms for plasminogen activating system members. Inhibition of Interleukin-1β (e.g. with Anakinra) may have potential as a novel treatment approach for the migration/invasion of endometriosis.Medicine, Faculty ofObstetrics and Gynaecology, Department ofReviewedFacultyGraduat