title: L-22 enhances the invasiveness of endometrial stromal cells of adenomyosis in an autocrine manner.
abstract: It has reported that interleukin-22 (IL-22) promotes the invasion of tumor cells. IL-22 in the endometriotic milieu stimulates the proliferation of human endometrial stromal cells (ESCs). The present study aimed to elucidate whether and how IL-22 regulates the invasion of ESCs from adenomyosis. The expression of IL-22 and its receptors in normal endometrium, eutopic endometrium and ectopic lesion was analyzed by immunohistochemistry; the invasiveness of ESCs in vitro was verified by Matrigel invasion assay; and the effects of IL-22 on the correspondent functional molecules were investigated by ELISA and flow cytometry. Here we found that IL-22 and its receptors IL-22R1 and IL-10R2 in eutopic endometrium and ectopic lesion of adenomyosis were significantly higher than that of normal endometrium. Recombinant human IL-22 (rhIL-22) increased IL-22R1 and IL-10R2 levels on ESCs. Moreover, rhIL-22 promoted the invasiveness of ESCs, and inhibited the expression of metastasis suppressor gene CD82, stimulated the secretion of IL-8, RANTES, IL-6 and VEGF of ESCs. On the contrary, the neutralizing antibody for IL-22 reversed these effects. Our current study has demonstrated that IL-22 has a positive feedback on the expression of its receptors IL-22R1 and IL-10R2 on ESCs. This autocrine effect of IL-22 promotes the invasion of ESCs possibly through regulating invasion-related molecules, suggesting that the abnormal high expression of IL-22 may play an important role in ESCs invasion and finally contribute to the origin and development of adenomyosis.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College Shanghai 200011, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College Shanghai 200011, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College Shanghai 200011, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College Shanghai 200011, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College Shanghai 200011, People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011, People's Republic of China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jin
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College Shanghai 200011, People's Republic of China.
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College Shanghai 200011, People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011, People's Republic of China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
mesh_terms: D062788:Adenomyosis / Q000378:metabolism* / Q000473:pathology; D019898:Autocrine Communication; D016022:Case-Control Studies; D002465:Cell Movement; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D051861:Kangai-1 Protein / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D018946:Chemokine CCL5; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D051861:Kangai-1 Protein; D018123:Receptors, Interleukin; D042461:Vascular Endothelial Growth Factor A; D000097043:Interleukin-22; C483024:CCL5 protein, human; C497688:CD82 protein, human; C508606:CXCL8 protein, human; C508600:IL6 protein, human; C467484:VEGFA protein, human; C415369:interleukin-22 receptor
keywords: IL-22; adenomyosis; endometrial stromal cells; invasion