Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis

摘要

Objective: To investigate interactions between peritoneal macrophages and endometrial stromal cells (ESCs) involved in the development of endometriosis. Design: Clinicopathologic and in vitro studies. Setting: Department of Obstetrics and Gynecology and Department of Pathology, Kumamoto University Hospital. Patient(s): Women undergoing laparoscopy or laparotomy to treat endometriosis or other benign gynecologic conditions. Intervention(s): We collected samples of peritoneal fluid (ascites), endometrium, and endometriotic tissues. We cocultured ESCs in vitro with or without human macrophages. Main Outcome Measure(s): Macrophage phenotypes in peritoneal fluid were determined via immunostaining. Proliferation of ESCs and activation of signal transducer and activator of transcription-3 (Stat3) in cocultures were evaluated. Result(s): The endometriosis group had a significantly higher total number of macrophages in ascites compared with the control group, but the ratios of CD163+ alternatively activated macrophages (M2) in the two groups did not differ significantly. Coculture with M2 macrophages significantly up-regulated ESC proliferation and Stat3 activation in ESCs in vitro. Proliferation of ESCs was suppressed after Stat3 was down-regulated by small interfering RNA. Stat3 was activated in epithelial cells and ESCs in human endometriotic lesions. Conclusion(s): Interactions between M2 macrophages and ESCs via Stat3 activation may play an important role in the development of endometriosis.