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

Capsule:
We demonstrate the significance of macrophages in the development of endometriosis and the involvement of signal transducer and activator of transcription-3 in interactions between endometrial stromal cells and macrophages.

Authors:
Fumiko Itoh, M.D., Yoshihiro Komohara, M.D., Ph.D., Kiyomi Takaishi, M.D., Ph.D., Rituo Honda, M.D., Ph.D., Hironori Tashiro, M.D., Ph.D., Satoru Kyo, M.D., Ph.D., Hidetaka Katabuchi, M.D., Ph.D., Motohiro Takeya, M.D., Ph.D.

Volume 99, Issue 6, Pages 1705-1713.e1, May 2013

Abstract:

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.

Patients:
Women undergoing laparoscopy or laparotomy to treat endometriosis or other benign gynecological conditions.

Interventions:
We collected samples of peritoneal fluid (ascites), endometrium, and endometriotic tissues. We co-cultured ESCs in vitro with or without human macrophages.

Main outcome measures:
Macrophage phenotypes in peritoneal fluid were determined via immunostaining. Proliferation of ESCs and activation of signal transducer and activator of transcription-3 (Stat3) in co-cultures were evaluated.

Results:
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. Co-culture with M2 macrophages significantly up-regulated ESC proliferation and Stat3 activation in ESCs in vitro. ESC proliferation was suppressed after Stat3 was down-regulated by small interfering RNA. Stat3 was activated in epithelial cells and ESCs in human endometriotic lesions.

Conclusions:
Interactions between M2 macrophages and ESCs via Stat3 activation may play an important role in the development of endometriosis.

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