Expression And Significance Of NF-κB And MIF In Endometriosis

Background Endometriosis ( EMs ) , occupying 30% of gynecological operations, is a kind of common and recurrent disease affecting 10-15% of the female population causing dysmenorrhea, dyspareunia, pelvic pain and infertility. Although the diagnosis of endometriosis may be suggested by the history and physical examination, its final diagnosis can only be acquired through laparoscopy. There are still no effective and specific chemical markers. Suppression of ovarian activity by hormonal therapy or operation, as the main therapeutic interventions today, can relieve symptoms and improve pregnant rate to some extend, but always with severe adverse effects and high relapse rate. No exact pathophysiology of this enigmatic disease is the principal reason that restrict its clinical and basic study. Up to now, the hypothesis of endometrium exfoliative fragments transplantation which Sampson put forward in 1925 has been accepted by most scholars. It mainly includes three stages: adhesion, invasion and angiogenesis, involve in numerous cytokines, enzymes, growth factors, and heredity, dyscrinism, immune function abnormity.Nuclear factor-kappaB(NF-κB), a key transcription factor in many kinds of cells, plays an important role in many biological processes such as inflammation and innate immunity, development, apoptosis, anti-apoptosis and vassular active factors in the processes of formation, growth, management and prognosis in many malignant tumor. But there is little research between NF-KB and endometriosis. It mainly includes three stages: adhesion, invasion and angiogenesis, involve in numerous cytokines, growth factors and so on. The abnormal activation of NF-κB can up-regulate such cytokines. Macrophage migration inhibitory factor(MIF)is one kind of multifunction cytokine. Lately researchers have made great progression in molecular pathogenesis of the disease. Some studies showed that MIF is the downstream and controlled gene of NF-κB, but their role in the pathogenesis of endometriosis is not clear yet. Section oneExpressions and correlation of nuclear factor-kappaB and macrophage migration inhibitory factor in endometriosisObjectives:To detect the expressions of nuclear factor-kappaB(NF-κB) and macrophage migration inhibitory factor (MIF) in normal endometrium(control group), ectopic endometrium and eutopic endometrium, investing the relationships of NF-κB and MIF with endometriosis(EMs), and evaluate the correlation between NF-κB and MIF expressions in EMs.Methods:Immuno-histochemistry way used to examine the NF-κB and MIF protein expression in 30 specimens of normal endometrium, 35 of eutopic endometrium of endometriosis and 60 of ectopic endometrium, and the results were analyzed with SPSS10. 0 statistical software.Results:⑴The expressions of NF-κB and MIF were predominantly found in the glandular epithelial cells of the 3 kinds of endometrium and partly found in stroma cell or vascular endothelial cell in eutopic ednometrium. It was significant to express differently in three groups, with the level of expression in ectopic endometriotic tissues the highest and in the normal endometrium the lowest (P<0. 01);⑵The expression levels of NF-κB, MIF in eutopic and ectopic endometrium has no cyclic change The expression levels of NF-κB and MIF in secretory phase endometrium in the proliferative phase endometrium were nearly (P>0.05);⑶The expression of NF-κB and MIF has some relation with the stage. The expression of NF-κB and MIF in stage II is strongest than other stages in eutopic endometrium, the expression of NF-κB and MIF in Stage II is stronger than Stage III, and the expression of NF-κB and MIF in Stage II is stronger than Stage IV;⑷There are positive correlation between NF-κB and MIF in the three kinds of endometrium The correlation coefficient are 0.875, 0.882 and 0.927.Conclusion:⑴NF-κB and MIF has abnormal higher expression in eutopic and ectopic endometrium of endometriosis patients, and there is litter expression in normal endometrium. These results demonstrate that NF-κB and MIF has some relation with endometriosis;⑵The expression of NF-κB and MIF has no cyclic change and play the role mainly in the early and mid-stages;⑶There are positive correlation between NF-κB and MIF, which show NF-κB may play role in endometriosis by up-regulate the expression of MIF. Section twoThe expression of MIF in endometrial stromal cells maybe via the nuclear transcription factor NF-κBObjectives:To detect the expressions of nuclear factor-kappaB(NF-κB) and macrophage migration inhibitory factor (MIF) in endometrial stromal cells(ESC) stimulated with TNF-αand PDTC+ TNF-αinvesting the relationships of NF-κB and MIF with endometriosis(EMs), and evaluate the correlation between NF-κB and MIF expressions in EMs.Methods: Primary culture the ESC exposed to TNF-α, PDTC+ TNF-αand detect the expressions of NF-κB and MIF in the culture supernatants by enzyme-linked immunosorbent assay (ELISA), and the results were analyzed with SPSS10.0 statistical software.Results:⑴NF-κB and MIF can express in the culture supernatants of the ESC;⑵There is a significant dose- and time-dependent increase in NF-κB and MIF secretion by ESC in response to tumour necrosis factor-alpha (TNF-α), and PDTC(a known NF-κB inhibitor)can inhibit the effect;⑶There are positive correlation between NF-κB and MIF in the culture supernatants of the ESC. The correlation coefficient is 0.947.Conclusion:⑴NF-κB and MIF can express in the culture supernatants of the ESC;⑵These results indicate clearly that TNF-αup-regulates the expression of MIF in endometrial stromal cells and PDTC inhibits the effect;⑶There are positive correlation between NF-κB and MIF in the culture supernatants of the ESC exposed to TNF-αand PDTC+ TNF-α, which show the expressions of MIF in endometrial stromal cells may via NF-κB pathway, and they may Play an important role in the physiology of the human endometrium.