The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls;n = ...The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls;n = 34) endometriosis during laparoscopy, the subcellular location and the percentages for TNF, TNFR1, TNFR2 and CD45 positive-cells were determined (immunohistochemistry);the protein concentration (ELISA) of the soluble receptors (sTNFR1 and sTNFR2) were measured in 4h-explants culture media and the TNF concentration was performed in ex vivo endometrial homogenates. The TNF, TNFR1 and TNFR2 mRNAs were analyzed by real-time PCR. In control endometria, TNF, TNFR1 and sTNFR1 proteins increased during the late secretory phase. In endometriosis endometria, the protein highest level of TNFR1 was reached during the early and the mid secretory phases and of sTNFR1 concentration during the proliferative phase;however, during the late secretory phase, both TNFR1 and sTNFR1 protein levels were reduced compared to the control endometria (p sTNFR2 concentrations, and TNF and TNFR2 mRNAs were similar in control and endometriosis endometria. Although TNFR1 mRNA was highly expressed, no significant differences were found between control and endometriosis endometria. In summary, this study establishes that TNF and TNFR1 protein expressions and the sTNFR concentrations in eutopic endometria from women with and without endometriosis are dependent on the menstrual cycle. The differences on the TNFR1 and sTNFR1 protein pattern between both groups, mainly during the mid and late secretory phases may play a role in the lower implantation rates observed in women with endometriosis, and also could be related to the altered cell death, which favor the augmented cell viability facilitating the characteristic endometrial implantation and growth outside the uterus in this disease.展开更多
Persistently high serum levels of soluble tumor-necrosis factor(TNF)receptor 2(sTNFR2)have been observed in septic shock and many inflammatory diseases.However,its origin and regulation during these pathological proce...Persistently high serum levels of soluble tumor-necrosis factor(TNF)receptor 2(sTNFR2)have been observed in septic shock and many inflammatory diseases.However,its origin and regulation during these pathological processes are still largely unknown.In this study,murine bone marrow(BM)chimeras selectively expressing TNFR2 on either BM-derived or non-BM-derived cells were generated and challenged with lipopolysaccharide(LPS).The results show that TNFR2 expression on non-BM-derived cells is crucial for both the sensitivity of mice to LPS and the downregulation of sTNFR2 in serum.Most importantly,sTNFR2 was released from both BM-and non-BM-derived cells.Non-BM TNFR1 expression influenced the sensitivity of mice to LPS challenge but not the level of serum sTNFR2.These results provide the first in vivo evidence for the origin and regulation of sTNFR2 in serum and could aid in the development of novel anti-TNF strategies against septic shock.展开更多
文摘The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls;n = 34) endometriosis during laparoscopy, the subcellular location and the percentages for TNF, TNFR1, TNFR2 and CD45 positive-cells were determined (immunohistochemistry);the protein concentration (ELISA) of the soluble receptors (sTNFR1 and sTNFR2) were measured in 4h-explants culture media and the TNF concentration was performed in ex vivo endometrial homogenates. The TNF, TNFR1 and TNFR2 mRNAs were analyzed by real-time PCR. In control endometria, TNF, TNFR1 and sTNFR1 proteins increased during the late secretory phase. In endometriosis endometria, the protein highest level of TNFR1 was reached during the early and the mid secretory phases and of sTNFR1 concentration during the proliferative phase;however, during the late secretory phase, both TNFR1 and sTNFR1 protein levels were reduced compared to the control endometria (p sTNFR2 concentrations, and TNF and TNFR2 mRNAs were similar in control and endometriosis endometria. Although TNFR1 mRNA was highly expressed, no significant differences were found between control and endometriosis endometria. In summary, this study establishes that TNF and TNFR1 protein expressions and the sTNFR concentrations in eutopic endometria from women with and without endometriosis are dependent on the menstrual cycle. The differences on the TNFR1 and sTNFR1 protein pattern between both groups, mainly during the mid and late secretory phases may play a role in the lower implantation rates observed in women with endometriosis, and also could be related to the altered cell death, which favor the augmented cell viability facilitating the characteristic endometrial implantation and growth outside the uterus in this disease.
基金grants from the National Natural Science Foundation of China(81030049 and 30700287).
文摘Persistently high serum levels of soluble tumor-necrosis factor(TNF)receptor 2(sTNFR2)have been observed in septic shock and many inflammatory diseases.However,its origin and regulation during these pathological processes are still largely unknown.In this study,murine bone marrow(BM)chimeras selectively expressing TNFR2 on either BM-derived or non-BM-derived cells were generated and challenged with lipopolysaccharide(LPS).The results show that TNFR2 expression on non-BM-derived cells is crucial for both the sensitivity of mice to LPS and the downregulation of sTNFR2 in serum.Most importantly,sTNFR2 was released from both BM-and non-BM-derived cells.Non-BM TNFR1 expression influenced the sensitivity of mice to LPS challenge but not the level of serum sTNFR2.These results provide the first in vivo evidence for the origin and regulation of sTNFR2 in serum and could aid in the development of novel anti-TNF strategies against septic shock.
