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

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.