title: 17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis.
abstract: Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of endometriosis has been demonstrated. Here we investigated the combined effect between 17β-estradiol (E2) and lipopolysaccharide (LPS) on pelvic inflammation and growth of endometriotic cells. Peritoneal fluid was collected from 46 women with endometriosis and 30 control women during laparoscopy. Peritoneal macrophages (Mφ) and stromal cells from eutopic/ectopic endometrial stromal cells (ESCs) were isolated from 10 women each with and without endometriosis in primary culture. Changes in cytokine secretion (interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α]) by Mφ and proliferation of ESCs in response to single and combined treatment with E2 and LPS were measured by enzyme-linked immunosorbent assay and by bromodeoxyuridine incorporation assay, respectively. A significantly increased secretion of IL-6 and TNF-α in Mφ culture media was found in response to E2 (10(-8) mol/L) compared to nontreated Mφ. This effect of E2 was abrogated after pretreatment of cells with ICI 182720 (10(-6) mol/L; an estrogen receptor [ER] antagonist). Combined treatment with E2 and LPS (10 ng/mL) additively promoted IL-6 and TNF-α secretion by peritoneal Mφ and growth of eutopic/ectopic ESCs. The additive effects of E2 + LPS on cytokine secretion and growth of ESCs were effectively suppressed after combined blocking of ER and Toll-like receptor 4. An additive effect was observed between E2 and LPS on promoting proinflammatory response in pelvis and growth of endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan nemokhan@nagasaki-u.ac.jp.
authors.forename: Khaleque Newaz
authors.initials: KN
authors.lastname: Khan
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Kitajima
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Gynecology, Saiseikai Nagasaki Hospital, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujishita
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Masuzaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004715:Endometriosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D004965:Estrogen Antagonists; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011960:Receptors, Estrogen; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol
keywords: LPS; endometriosis; estradiol; macrophages; stromal cells