title: IL-17A Contributes to the Pathogenesis of Endometriosis by Triggering Proinflammatory Cytokines and Angiogenic Growth Factors.
abstract: Endometriosis is a chronic, inflammatory disease characterized by the growth of endometrial tissue in aberrant locations outside the uterus. Neoangiogenesis or establishment of new blood supply is one of the fundamental requirements of endometriotic lesion survival in the peritoneal cavity. IL-17A is emerging as a potent angiogenic and proinflammatory cytokine involved in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. However, sparse information is available in the context of endometriosis. In this study, we demonstrate the potential importance of IL-17A in the pathogenesis and pathophysiology of endometriosis. The data show a differential expression of IL-17A in human ectopic endometriotic lesions and matched eutopic endometrium from women with endometriosis. Importantly, surgical removal of lesions resulted in significantly reduced plasma IL-17A concentrations. Immunohistochemistry revealed localization of IL-17A primarily in the stroma of matched ectopic and eutopic tissue samples. In vitro stimulation of endometrial epithelial carcinoma cells, Ishikawa cells, and HUVECs with IL-17A revealed significant increase in angiogenic (vascular endothelial growth factor and IL-8), proinflammatory (IL-6 and IL-1β), and chemotactic cytokines (G-CSF, CXCL12, CXCL1, and CX3CL1). Furthermore, IL-17A promoted tubulogenesis of HUVECs plated on Matrigel in a dose-dependent manner. Thus, we provide the first evidence, to our knowledge, that endometriotic lesions produce IL-17A and that the removal of the lesion via laparoscopic surgery leads to the significant reduction in the systemic levels of IL-17A. Taken together, our data show a likely important role of IL-17A in promoting angiogenesis and proinflammatory environment in the peritoneal cavity for the establishment and maintenance of endometriosis lesions.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L 3N6, Canada;
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L 3N6, Canada;
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Edwards
authors.affiliation: Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario K1H 7W9, Canada;
authors.forename: Sukhbir S
authors.initials: SS
authors.lastname: Singh
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC 27514; and.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
authors.affiliation: Department of Obstetrics and Gynecology, Greenville Health System, Greenville, SC 29605.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L 3N6, Canada; tayadec@queensu.ca.
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Tayade
mesh_terms: D000328:Adult; D002460:Cell Line; D054428:Chemokine CX3CL1 / Q000096:biosynthesis; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D016889:Endometrial Neoplasms / Q000378:metabolism; D004715:Endometriosis / Q000276:immunology* / Q000473:pathology; D004717:Endometrium / Q000098:blood supply / Q000276:immunology / Q000473:pathology* / Q000601:surgery*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D010535:Laparoscopy; D009389:Neovascularization, Pathologic / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D055815:Young Adult
chemical_list: C515538:CX3CL1 protein, human; C475829:CXCL1 protein, human; C515255:CXCL12 protein, human; C508606:CXCL8 protein, human; D054428:Chemokine CX3CL1; D054360:Chemokine CXCL1; D054377:Chemokine CXCL12; C508717:IL17A protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor