title: Interleukin (IL)-17A stimulates IL-8 secretion, cyclooxygensase-2 expression, and cell proliferation of endometriotic stromal cells.
abstract: IL-17A is secreted from Th17 cells, a discovery leading to revision of the mechanism underlying the role of Th1/Th2 in the immune response. Strong evidence suggests that immune responses associated with inflammation are involved in the pathogenesis of endometriosis. In the present study, we first demonstrated that the presence of Th17 cells in peritoneal fluid of endometriotic women by flow cytometric analysis and IL-17A-positive cells in endometriotic tissues by immunohistochemistry. To investigate the role of IL-17A in the development of endometriosis, we then studied the effect of IL-17A on IL-8 production, cyclooxygensase-2 expression, and cell proliferation of cultured endometriotic stromal cells (ESCs). IL-17A enhanced IL-8 secretion from ESCs in a dose-dependent manner. The IL-17A-induced secretion of IL-8 from ESCs was suppressed by anti-IL-17 receptor A antibodies or inhibitors of p38 MAPK, p42/44 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase. Addition of TNFalpha synergistically increased IL-17A-induced IL-8 secretion from ESCs. IL-17A also enhanced the expression of cyclooxygensase-2 mRNA and proliferation of ESCs. IL-17A may play a role in the development of endometriosis by stimulating inflammatory responses and proliferation of ESCs.
authors: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Tetsuya
authors: T
authors: Hirata
authors: Yutaka
authors: Y
authors: Osuga
authors: Kahori
authors: K
authors: Hamasaki
authors: Osamu
authors: O
authors: Yoshino
authors: Mika
authors: M
authors: Ito
authors: Akiko
authors: A
authors: Hasegawa
authors: Yuri
authors: Y
authors: Takemura
authors: Yasushi
authors: Y
authors: Hirota
authors: Emi
authors: E
authors: Nose
authors: Chieko
authors: C
authors: Morimoto
authors: Miyuki
authors: M
authors: Harada
authors: Kaori
authors: K
authors: Koga
authors: Toshiki
authors: T
authors: Tajima
authors: Shigeru
authors: S
authors: Saito
authors: Tetsu
authors: T
authors: Yano
authors: Yuji
authors: Y
authors: Taketani
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004715:Endometriosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000888:Antibodies, Anti-Idiotypic; C508717:IL17A protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D020929:Mitogen-Activated Protein Kinase Kinases