The Pertinence Of MMP-2、IL-4 And IFN-γ In Endometriosis

Objective: Matrix Metalloproteinase-2(MMP-2) plays a vital role in the development of endometriosis, and Th1/Th2 immune imbalance also participates in endometriosis progression. Recent studies showed that MMP-2 promoted the development of melanoma through inducing Th2 cells differentiation. However, few studies have determined the relationship between Th1/Th2 and MMP-2 in endometriosis. As transcription of Th1 and Th2 cells, T-bet and GATA-3 can regulate the generation of IFN-γ and IL-4, which represent Th1 and Th2 cells specific cytokine respectively. In the study, we detected the expression of IL-4、IFN-γ、T-bet、GATA-3、MMP-2 in ectopic endometrial tissues and endometrial tissues, and explore the relationship between Th1/Th2 drift and MMP-2 from the level of cytokines and transcriptions and its effects on the development of endometriosis. We sought these data for the prevention and treatment of endometriosis.Methods:1 Samples were collected in 60 cases of ectopic endometrial tissues and 57 cases of endometrial tissues from the Department of Obstetrics and Gynecology of Tangshan Gongren Hospital, Hebei Medical University, Tangshan, China between March 2013 and March 2014.2 Real-time RT-PCR method was adopted for measuring MMP-2 m RNA, IL-4 m RNA and IFN-γ m RNA expression level in samples.3 The expression of MMP-2 was detected by immunohistochemistry method and gelatinase activity was detected by zymography in ectopic endometrial tissues and endometrial tissues.4 Western blot method was adopted to detect T-bet and GATA-3 expression in ectopic endometrial tissues and endometrial tissues.5 SPSS13.0 statistical software was used for statistical analyses. Data gained from Real-time PCR analyses were identified by one-way ANOVA and moderated t test. Spearman rank correlation coefficient was used to analyze bivariate correlation. All experiments were repeated at least three times. Data were presented as mean±SD. Differences with P<0.05 were considered significant.Results:1 The expression of MMP-2 in endometrial tissuesThe results getting from real-time RT-PCR showed that the expression of MMP-2 m RNA was higher in ectopic endometrial tissues than that of endometrial tissues, and there was a significant difference of MMP-2 m RNA between the endometriosis group and the control group(P < 0.05). The MMP-2 m RNA expressed stronger in endometriosis phase I to II than that in phase III to IV(P < 0.05). Tissues in groups were analyzed by immunohistochemistry, the results shows MMP-2 expression in endometriosis was higher than that in control. The results from zymography shows that the gelatinase activity was stronger in endometriosis than that in control, and the gelatinase activity in endometriosis phase I to II was stronger than that in phase III to IV.2 The expression of IL-4 and IFN-γ in endometrial tissuesIn the study, IL-4 presented Th2 cells while IFN-γ presented Th1 cells. The levels of IL-4 m RNA and IFN-γ in tissues were detected by RT-PCR, and the values were calculated by division, which was regarded as the level of Th2/Th1 drift, and then explored the relationship between the ratio and MMP-2 and its effect on endometriosis. The results indicated that the expression IL-4 m RNA in endometriosis was higher than that in control, and the IL-4 m RNA expressed stronger in endometriosis phase I to II than that in phase III to IV, and the differences were statistically significant(P<0.05). The expression of IFN-γ m RNA in ectopic endometrial tissues was less than that in normal endometrial tissues, and the IL-4 m RNA expressed stronger in endometriosis phase I to II than that in phase III to IV, the differences were significant statistically(P<0.05). The ratio of IL-4/IFN-γ in endometriosis was higher than that in control, and in endometriosis, the ratio was higher in phase I to II than that in phase III to IV(P<0.05).3 The expression of T-bet and GATA-3 in endometrial tissuesT-bet is Th1 cells specific transcription while GATA-3 is Th2 cells’. To study their effect on endometriosis, we detected their expression on tissues. The results shows that compared with control group, the ectopic endometrial tissues expressed T-bet less and GATA-3 more, and in endometriosis, the T-bet expressed less in phase I to II than that in phase III to IV, while GATA-3 expressed more in phase I to II than that in phase III to IV.4 The correlation of Th1, Th2 related factors and MMP-2According to Spearman correlation analysis, the MMP-2 m RNA expression level was positively correlated to IL-4, and negatively correlated with IFN-γ.Conclusions:1 The high expression of MMP-2 was one of the causes in the occurrence and development of endometriosis.2 In ectopic endometrial tissues, there was Th1/Th2 immune balance deviation, which may play an important role in the occurrence and development of endometriosis.3 The expression of MMP-2 is positive correlation to IL-4 expression and negative correlation to IFN-γ m RNA expression in ectopic endometrial tissues.