Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway

Objective. This study investigated the alterations in macrophage polarization in patients with endometriosis as well as the underlying molecular mechanisms. Methods. Peritoneal washings, serum samples, and endometrial tissues were collected from endometriosis patients and control subjects. Endometri...

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Main Authors: Mei-Fang Nie, Qi Xie, Ya-Hong Wu, Hua He, Lu-Jie Zou, Xiao-Ling She, Xian-Qing Wu
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/6285813
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author Mei-Fang Nie
Qi Xie
Ya-Hong Wu
Hua He
Lu-Jie Zou
Xiao-Ling She
Xian-Qing Wu
author_facet Mei-Fang Nie
Qi Xie
Ya-Hong Wu
Hua He
Lu-Jie Zou
Xiao-Ling She
Xian-Qing Wu
author_sort Mei-Fang Nie
collection DOAJ
description Objective. This study investigated the alterations in macrophage polarization in patients with endometriosis as well as the underlying molecular mechanisms. Methods. Peritoneal washings, serum samples, and endometrial tissues were collected from endometriosis patients and control subjects. Endometrial stromal cells (ESCs) were isolated from endometrial tissue, and conditioned medium was prepared by treating ESCs with or without various concentrations of interleukin- (IL-) 6, estrogen, or progestin. The frequencies of CD86+ and CD163+ cells and expression levels of these markers as well as the cytokines IL-12 and IL-10 were measured in THP-1- (human monocytic leukemia cell) derived macrophages. Results. There was a decrease in the percentage of CD86+ macrophages in the peritoneal wash solution of patients with endometriosis. Ectopic endometrial homogenates could promote M1 to M2 macrophage polarization in response to lipopolysaccharide (LPS), as evidenced by the increased percentage of CD163+ macrophages and increased IL-10 expression as well as a decreased percentage of CD86+ cells and lower IL-12 expression. In contrast, addition of serum from women with endometriosis to THP-1 cells resulted in the polarization of macrophages towards both M1 and M2 phenotypes. Upregulation of Smad2/Smad3 in macrophages upon exposure to eutopic and ectopic endometrial homogenates as well as serum of women with endometriosis was observed, and blockage of Smad2/Smad3 with their inhibitor SB431542 could reverse the macrophage polarization from M1 to M2. Conditioned medium induced by IL-6, but neither estrogen nor progestin, could facilitate M2 polarization. Neutralization of IL-6 diminished macrophage M2 polarization in endometriosis. Conclusion. This study provides detailed evidence supporting alterations in M1 to M2 macrophage polarization that may contribute to the initiation as well as progression of endometriosis.
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spelling doaj-art-50671db4e9fe4a19adda70be367a4e752025-08-20T02:05:10ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/62858136285813Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 PathwayMei-Fang Nie0Qi Xie1Ya-Hong Wu2Hua He3Lu-Jie Zou4Xiao-Ling She5Xian-Qing Wu6Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 4100011, ChinaDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 4100011, ChinaDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 4100011, ChinaDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 4100011, ChinaDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 4100011, ChinaDepartment of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 410011, ChinaDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 4100011, ChinaObjective. This study investigated the alterations in macrophage polarization in patients with endometriosis as well as the underlying molecular mechanisms. Methods. Peritoneal washings, serum samples, and endometrial tissues were collected from endometriosis patients and control subjects. Endometrial stromal cells (ESCs) were isolated from endometrial tissue, and conditioned medium was prepared by treating ESCs with or without various concentrations of interleukin- (IL-) 6, estrogen, or progestin. The frequencies of CD86+ and CD163+ cells and expression levels of these markers as well as the cytokines IL-12 and IL-10 were measured in THP-1- (human monocytic leukemia cell) derived macrophages. Results. There was a decrease in the percentage of CD86+ macrophages in the peritoneal wash solution of patients with endometriosis. Ectopic endometrial homogenates could promote M1 to M2 macrophage polarization in response to lipopolysaccharide (LPS), as evidenced by the increased percentage of CD163+ macrophages and increased IL-10 expression as well as a decreased percentage of CD86+ cells and lower IL-12 expression. In contrast, addition of serum from women with endometriosis to THP-1 cells resulted in the polarization of macrophages towards both M1 and M2 phenotypes. Upregulation of Smad2/Smad3 in macrophages upon exposure to eutopic and ectopic endometrial homogenates as well as serum of women with endometriosis was observed, and blockage of Smad2/Smad3 with their inhibitor SB431542 could reverse the macrophage polarization from M1 to M2. Conditioned medium induced by IL-6, but neither estrogen nor progestin, could facilitate M2 polarization. Neutralization of IL-6 diminished macrophage M2 polarization in endometriosis. Conclusion. This study provides detailed evidence supporting alterations in M1 to M2 macrophage polarization that may contribute to the initiation as well as progression of endometriosis.http://dx.doi.org/10.1155/2018/6285813
spellingShingle Mei-Fang Nie
Qi Xie
Ya-Hong Wu
Hua He
Lu-Jie Zou
Xiao-Ling She
Xian-Qing Wu
Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway
Journal of Immunology Research
title Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway
title_full Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway
title_fullStr Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway
title_full_unstemmed Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway
title_short Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway
title_sort serum and ectopic endometrium from women with endometriosis modulate macrophage m1 m2 polarization via the smad2 smad3 pathway
url http://dx.doi.org/10.1155/2018/6285813
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