title: IL-22 in the endometriotic milieu promotes the proliferation of endometrial stromal cells via stimulating the secretion of CCL2 and IL-8.
abstract: Interleukin-22 (IL-22) is a member of the IL-10 cytokine family and plays critical roles in inflammation, immune surveillance, and tissue homeostasis. However, whether IL-22 regulates the growth of endometrial stromal cells (ESCs), and participates in the pathogenesis of endometriosis remain unclear. In this study, we found that the expression of IL-22 and it receptors (IL-22R1 and IL-10R2) in eutopic endometrium and ectopic lesion of women with endometriosis was higher than that from healthy control. Recombinant human IL-22 (rhIL-22) stimulated the proliferation of ESCs in a dosage-dependent manner. On the contrary, anti-human IL-22 neutralizing antibody inhibited the proliferation of ESCs in vitro. The stimulatory effect of IL-22 on the proliferation of ESCs could be reversed by inhibitor of STAT5, ERK1/2 or AKT signal pathway. However, blocking STAT3, JNK or P38 signal pathway had no these effects. By Enzyme-linked immunosorbent assay (ELISA) and flow cytometry assay, we demonstrated the rhIL-22 not only stimulate the secretion of CCL2 and IL-8, but also significantly up-regulate the expression of IL-8 receptor CXCR1 on ESCs. Meanwhile, STAT5, ERK1/2 and or AKT signal inhibitors could abrogate the increase of CCL2, IL-8 and CXCR1 levels induced by rhIL-22. However, rhIL-22 had not similar influence on CCL2 receptor CCR2. Our current results suggested that the higher level of IL-22 and it receptors in eutopic endometrium may stimulate the expression of CCL2, IL-8/CXCR1, and further promote the growth of ESCs possibly through activating STAT5, MAPK/ERK1/2 and or AKT signal pathways, which may be involved in the occurrence and development of endometriosis.
authors.affiliation: Department of Pathology, Yixing Second People's Hospital Yixing, Jiangsu Province 214221, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Liu
authors.forename: Kai-Kai
authors.initials: KK
authors.lastname: Chang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D018932:Chemokine CCL2; D016209:Interleukin-8; D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22; C415369:interleukin-22 receptor
keywords: CCL2; IL-22; IL-8; endometrial stromal cells; endometriosis; proliferation