4.7 Article

Interleukin-17A is present in neutrophils in endometrioma and stimulates the secretion of growth-regulated oncogene-α (Gro-α) from endometrioma stromal cells

Journal

FERTILITY AND STERILITY
Volume 98, Issue 5, Pages 1218-+

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2012.07.1117

Keywords

Endometriosis; cytokine; inflammation; immunology; neutrophils; Gro-alpha

Funding

  1. Ministry of Health, Labour and Welfare
  2. Ministry of Education, Culture, Sports, Science and Technology
  3. Yamaguchi Endocrine Research Foundation
  4. Grants-in-Aid for Scientific Research [23592395, 24791689, 23791813] Funding Source: KAKEN

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Objective: To investigate a new role of interleukin (IL)-17A in endometriosis. Design: Laboratory study. Setting: University hospital. Patient(s): Patients with ovarian endometrioma undergoing laparoscopy or laparotomy. Intervention(s): Primary culture of endometrioma stromal cells (EoSCs) was stimulated with IL-17A. Sections of endometrioma tissue were immunostained with antibodies for IL-17A, growth- regulated oncogene-alpha (Gro-alpha), and elastase, a marker of neutrophils. They were also examined with immunofluorescent double staining for IL-17A and myeloperoxidase, another marker of neutrophils. Main Outcome Measure(s): Concentration of Gro-alpha was measured using a specific ELISA. Neutrophil chemotaxis was measured with Boyden chamber method. Immunostained sections were examined under microscope. Result(s): Interleukin-17A increased the secretion of Gro-alpha from EoSCs dose-dependently. The conditioned medium of EoSCs stimulated with IL-17A attracted more neutrophils than that of EoSCs stimulated with vehicle, and the increase was inhibited by the addition of Gro-alpha-neutralizing antibody. On immunostaining, IL-17A and Gro-alpha were detected in similar areas of the stroma beneath the epithelium, where Gro-alpha was detected in cells with a stromal cell appearance whereas IL-17A was detected in neutrophils as determined by detection of elastase. Fluorescent immunostaining corroborated that myeloperoxidase-positive neutrophils were also positive for IL-17A. Conclusion(s): It is suggested that IL-17A produced by neutrophils stimulates Gro-alpha secretion from EoSCs, thereby recruiting more neutrophils and inducing perpetuating inflammation in endometriosis. Fertil Steril (R) 2012;98:1218-24. (C) 2012 by American Society for Reproductive Medicine.)

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