title: Combined 17β-Estradiol with TCDD Promotes M2 Polarization of Macrophages in the Endometriotic Milieu with Aid of the Interaction between Endometrial Stromal Cells and Macrophages.
abstract: The goal of this study is to elucidate the effects of 17β-estradiol and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on macrophage phenotypes in the endometriotic milieu. Co-culture of endometrial stromal cells (ESCs) and U937 cells (macrophage cell line) was performed to simulate the endometriotic milieu and to determine the effects of 17β-estradiol and/or TCDD on IL10, IL12 production and HLA-DR, CD86 expression by U937 macrophages. We found that combining 17β-estradiol with TCDD has a synergistic effect on inducing M2 activation when macrophages are co-cultured with ESCs. Moreover, the combination of 17β-estradiol and TCDD significantly enhanced STAT3 and P38 phosphorylation in macrophages. Differentiation of M2 macrophages induced by 17β-estradiol and TCDD were effectively abrogated by STAT3 and P38MAPK inhibitors, but not by ERK1/2 and JNK inhibitors. In conclusion, 17β-estradiol and TCDD in the ectopic milieu may lead to the development of endometriosis by inducing M2 polarization of macrophages through activation of the STAT3 and P38MAPK pathways.
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: NingLing
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: HaiYan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Yonglun
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Songguo
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Ai
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Lyu
authors.affiliation: Department of Assisted Reproduction, Shanghai ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Kuang
mesh_terms: D000328:Adult; D002460:Cell Line; D018920:Coculture Techniques; D004357:Drug Synergism; D004715:Endometriosis / Q000209:etiology* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004958:Estradiol