title: The high level of RANTES in the ectopic milieu recruits macrophages and induces their tolerance in progression of endometriosis.
abstract: RANTES (C-C chemokine, regulated on activation, normal T cell expressed and secreted) is involved in progression of endometriosis, but the precise mechanism is understood inadequately. This study is to elucidate the roles of RANTES in macrophage recruitment and tolerance in the endometriotic milieu. The expression of RANTES was analyzed by immunohistochemistry. The cell co-cultures were applied to simulate the endometriotic milieu to investigate the regulation of RANTES secretion and its receptor CCR1 expression. Transwell migration assay was used for chemotaxis of U937 cells (macrophage line) to endometrial stromal cells (ESCs) and/or human pelvic mesothelial cells. The expression of CCR1 was analyzed by RT-PCR and qPCR in transcription and by western blot in translation respectively. Concentrations of RANTES, IL10, and IL12p70 were determined by ELISA. The phenotype of U937 cells and apoptosis of ESCs were analyzed by flow cytometry. We have found that the expression of RANTES is significantly higher in the endometriotic tissue and eutopic endometrium than that of the normal endometrium without endometriosis. The combination of 17β-estradiol and dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin increases significantly RANTES secretion in the endometriosis-associated cell co-culture which can recruit more macrophages, upregulate CCR1 expression, and induce tolerant phenotype, which inhibits the apoptosis of ESC in the milieu. In conclusion, the higher levels of RANTES in the ectopic milieu facilitate the onset and progression of endometriosis by macrophage recruitment and tolerance that in turn inhibits apoptosis and enhances growth of ESC.
authors: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai 200011, People's Republic of China.
authors: Xiao-Qiu
authors: XQ
authors: Wang
authors: Jing
authors: J
authors: Yu
authors: Xue-Zhen
authors: XZ
authors: Luo
authors: Ying-Li
authors: YL
authors: Shi
authors: Yun
authors: Y
authors: Wang
authors: Ling
authors: L
authors: Wang
authors: Da-Jin
authors: DJ
authors: Li
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001202:Ascitic Fluid / Q000737:chemistry / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D018946:Chemokine CCL5 / Q000378:metabolism*; D004715:Endometriosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology; D020298:U937 Cells
chemical_list: D051940:B7-2 Antigen; D018946:Chemokine CCL5; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D000072317:Polychlorinated Dibenzodioxins; D054389:Receptors, CCR1; D016753:Interleukin-10; D018664:Interleukin-12; D004958:Estradiol