Study Of The Effects Of IL-17 And IL-17RA On Endometriosis And Its Mechanism

Objectives To investigate the role of interleukin(IL)-17 A and its receptor A( IL-17RA)in endometriosis and assess IL-17-driven inflammatory responses, so as to explore the mechanism of IL-17A/IL-17 RA on endometriosis.Methods Twenty-four healthy, virgin, female Sprague Dawley rats(approximately weighing 180~200g and aged 8 weeks) were randomly allocated into three groups:endometriosis group(EMs, which is surgically created by autotransplanting pieces of uterine horn), sham-operation group(sham, similar to EMs except transplanting pieces of fat tissue surrounding the uterine horn uterine horn instead of pieces of uterine horn) and control group. Real-time PCR and ELISA and Western blotting were performed to indentify the IL-17 A and IL-17 RA m RNA and protein. JNK1/2、p-JNK1/2、ERK1/2、pERK1/2、MMP-9、MMP-7、MMP-2、cyclin D1、Bcl-2、Bax、VEGF、VEGFR1proteins were detected by Western blotting, and immunohistochemistry was carried for CD31 staining to detect microvessel density(MVD).Results The levels of IL-17 A and IL-17 receptor A(IL-17RA) were the highest in rat ectopic endometrial tissue, followed by eutopic endometrial tissue, sham group and control group(p<0.05). The increased levels of IL-17 A and IL-17 RA were accompanied with increased IL-17-driven inflammatory responses, including activation of c-Jun N-terminal kinase(JNK)1/2 and extracellular signal-regulated kinase(ERK)1/2 pathways, increase in expression of several matrix metalloproteinases(MMP9, MMP7, MMP2), cyclin D1, Bcell lymphoma(Bcl-2), and decrease in Bcl-2-associated X protein(Bax) expression, and increase in expression of vascular endothelial growth factor(VEGF) and VEGF receptor1(VEGFR1) protein which were associated with increased angiogenesis. The MVD in ectopic endometrial tissue was significantly higher that in eutopic and control endometrial tissue.Conclusions IL-17 A and IL-17 RA increased in ectopic endometrial tissue, and JNK1/2and ERK1/2 signaling pathway was activated, and several IL-17A/IL-17 RA downstream proteins were differentially expressed in ectopic endometrial tissue, and angiogenesis increased, suggesting that IL-17 and its signaling pathways appear as promising new targets in the design and development of drugs for endometriosis prevention and treatment.