| BackgroundEndometriosis(EM)is a chronic estrogen-dependent inflammatory gynecologic disease characterized by the colonization and growth of endometrial glands and mesenchyme outside the uterine cavity,which can cause chronic pelvic pain and infertility.Its etiology is unclear,and there is now a view that the development of endometriosis is closely related to Escherichia coli(E.coli).Several studies have shown that the reproductive microbiota of patients with endometriosis differs from that of controls,with E.coli being the most common of the differing species.These studies were all conducted after the onset of endometriosis.Endometriosis can also lead to changes in the microbiota.Therefore,the causal relationship between endometriosis and the increase of E.coli is not yet determined.Evidence suggests a close association between development of endometriosis and immune cells,especially in terms of the role of macrophages.According to the different functional states of macrophages,they can be classified into two types:M1(pro-inflammatory)and M2(anti-inflammatory).Ml macrophages can simultaneously promote local immune cell aggregation in ectopic lesions by releasing various cytokines,such as interleukin-1β(IL-1β)and tumor necrosis factor-alpha(TNF-α),to induce an inflammatory state and inhibit lesion growth.Contrastingly,M2 macrophages can release vascular endometrial growth factor(VEGF)and IL-10 to promote neuroangiogenesis and EM lesion growth.Escherichia coli can play an important role in different diseases by inducing macrophage polarization,but in different disease models,the result of macrophage polarization is different.At present,the effect of E.coli on macrophage polarization in endometriosis remains to be studied.ObjectivesThe purpose of this study was to explore the influence of increased E.coli on the growth of endometriosis lesions,and clarify the induction effect of E.coli on the polarization of disease-related abdominal macrophages.MethodsThe phagocytosis of induced macrophage to mice endometrial stromal cells was detected by cell co-culture system.The medium for co-culture of induced macrophages and mouse endometrial stromal cells was collected and used as conditioned medium to stimulate the endometrial cells.The migration and proliferation of endometrial stromal cells in conditioned medium was measured by cell wounding heal,Transwell test and CCK-8.The role of IL-1β in promoting endometrial proliferation and migration was verified by siRNA gene knockout technique.The effect of E.coli on lesion growth was verified by mouse endometriosis modeling technique,and mouse abdominal macrophage polarization was detected by flow cytometry.The phagocytic ability of peritoneal macrophages was detected by intraperitoneal injection of endometrial cells.CCR2 inhibitors was used to reduce the aggregation of bone marrow-derived macrophages into the abdominal cavity.The growth of the lesion and the polarization of mouse peritoneal macrophage were detected.Results1.E.coli induced RAW264.7 polarize to M1,which inhibited the proliferation and migration of endometrial stromal cells,while blocking induced macrophages secrete IL-1βcould eliminate the inhibition.2.The volume of endometriosis lesions in E.coli-group was lower than PBS-group.The proportion of M1 in SpM and total peritoneal macrophages increased,and the phagocytosis of peritoneal macrophages was enhanced.3.The use of CCR2 inhibitors could eliminate the differences in the volume of lesions between E.coli-group and PBS-group,and the M1 in peritoneal macrophage of E.coli-group was reduced compared with the PBS-group.Conclusions1.E.coli can induce the polarization of macrophages towards M1 macrophages,and induced macrophages can inhibit the growth of mice endometrial primary cells through IL-1β.2.E.coli inhibited the growth of endometriosis lesions in mice.The proportion of M1 in total peritoneal macrophages of mice increased.3.The inhibition of E.coli on the growth of endometriosis lesions was related to macrophages from bone marrow. |
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