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4 October 2017 Interleukin 6 secretion from alternatively activated macrophages promotes the migration of endometriotic epithelial cells
Jeong-Hwa Woo, Yeong-In Yang, Ji-Hye Ahn, Youn Seok Choi, Jung-Hye Choi
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Abstract

Accumulating evidence has suggested an interaction between endometriotic cells and macrophages in the endometriotic microenvironment and the potential role of this interaction in the pathogenesis of endometriosis. However, how endometriotic cells communicate with macrophages to influence their function is poorly understood. In the present study, we found that the mRNA expression and production of CC chemokine ligand 2 (CCL2) were much higher in human endometriotic epithelial cells (11Z and 12Z) than those in human endometrial epithelial cells (HES). The inhibition of CCL2 action using neutralizing antibodies substantially suppressed macrophage migration induced by endometriotic epithelial cells. The endometriosis-associated macrophages (EAMs), which are the macrophages that are stimulated by the conditionedmedium (CM) of human endometriotic cells, highly expressed the M2 phenotype markers (MRC1 and TREM2). In addition, the CM of EAMs significantly increased cell migration in 12Z cells, but no significant change was observed in cell growth. RT-PCR and antibody array analyses revealed that EAMs highly express and produce interleukin (IL) 6 compared to macrophages stimulated by the CM of HES cells. Moreover, the EAM-CM-induced migration and MMP2/9 expression in endometriotic cells were significantly attenuated by IL6 signaling inhibition. These results suggest a reciprocal activation of macrophages and endometriotic cells via the soluble factors CCL2 and IL6, which may contribute to the development of endometriosis.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Jeong-Hwa Woo, Yeong-In Yang, Ji-Hye Ahn, Youn Seok Choi, and Jung-Hye Choi "Interleukin 6 secretion from alternatively activated macrophages promotes the migration of endometriotic epithelial cells," Biology of Reproduction 97(5), 660-670, (4 October 2017). https://doi.org/10.1093/biolre/iox118
Received: 4 April 2017; Accepted: 26 September 2017; Published: 4 October 2017
JOURNAL ARTICLE
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KEYWORDS
CCL2
endometriosis
Il6
macrophages
MMP2/9
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