In the present study, the effect of blockage of the costimulatory signal CD86 at time of implantation on the expressions of TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins at the maternal-fetal interface and the outcome of ...In the present study, the effect of blockage of the costimulatory signal CD86 at time of implantation on the expressions of TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins at the maternal-fetal interface and the outcome of pregnancy in mufine abortion-prone model was investigated, in which the CBA/J × DBA/2 matings were used as the abortion-prone model and the CBA/J × BALB/c matings used as the normal pregnant model. The study was performed in following three groups： 2 groups of the abortion-prone model, which were experimental group and control experimental group, and 1 group of normal pregnant model, and each group had 10 pregnant CBA/J mice exclusively. Female pregnant CBA/J mice in the experimental group received an intraperitoneal （i. p. ） injection of 100μg of antimouse CD86 mAb in 200 μl of PBS at day 4.5 of gestation, and the irrelevant-isotope matched rat IgG2b was administrated in the control experimental group with the same dosage and at same time. For the normal pregnant group, no treatment was given. The pregnant CBA/J mice were killed on day 13.5 of gestation. Then, the embryo resorption rate was calculated and the expressions of TGF-β1, MMP-9, TIMP3 and PAI-1 were detected by using immunohistochemical methods. It was demonstrated that the embryo resorption rate in the experimental group was significantly reduced in comparison with that in the control experimental group （X^2 = 7.441, P = 0.006）, but there was no significant difference with that in normal pregnant group （X^2 = 0.016, P = 0.898）. The expressions of TGF-β1 and PAI-1 in the experimental group were significantly increased in comparison with that in the control experimental group （P =0.010, P = 0.003, respectively）, with no significant difference from that in the nonnal pregnant group （P = 0.500）. However, the expression of MMP-9 in the experimental group was significantly reduced in comparison with that in the control experimental group （P = 0.012） with no significant difference from that in the normal pregnant group （P = 0.500）. The expression of TIMP-3 in the experimental group showed no significant difference both with the control experimental group （ P = 0. 328） and the normal pregnant group （ P = 0. 500）. It is concluded that the blockage of the costimulatory molecule CD86 at early stage of gestation can render TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins to express their immuno-tolerant effects through their characteristic pathways and induce the reduction of the embryo resorption rate in the natural abortion-prone model of mice to the level of normal pregnancy.展开更多
Background Inhibition of the key costimulatory signals results in T cell anergy, indicating the alloantigen-specific immunologic unresponsiveness. In this study, the effect of blockage of costimulatory signal CD86 on ...Background Inhibition of the key costimulatory signals results in T cell anergy, indicating the alloantigen-specific immunologic unresponsiveness. In this study, the effect of blockage of costimulatory signal CD86 on murine abortion-prone model was studied. Methods Thirty CBA/J female mice cohabitated with DBA/2 male or BALB/c male mice were investigated. CBNJ xDBN2 matings were used as the abortion-prone model, and CBA/J × BALB/c matings were used as the normal pregnant model. The abortion-prone models were divided into experimental and control groups, and the normal pregnant models were set as a normal group （10 mice in each group）. The mice in the experimental group were treated with anti-mouse CD86 monoclonal antibody （mAb） （100 μg） on day 4.5 of gestation, while the controls received irrelevant-isotype matched rat IgG2b. As for the normal group, nothing was given to the mice. The mice were killed on day 13.5 of gestation, embryo resorption rate and the expression of transforming growth factor β1 （TGF-β1）, plasminogen activator inhibitor 1 （PAI-1）, and matrix metalloproteinase 9 （MMP-9） were detected. Then the data were analyzed by Chi-square test and Fisher＇s exact test. Results The embryo resorption rate in the experimental （8.2%） and normal groups （7.7%） was significantly lower than that of the control （23.5%, P〈0.05）. No significant difference was detected between the experimental and normal groups （P〉0.05）. The positive expression rates of TGF-β1 and PAl-1 proteins in the experimental and normal groups were significantly higher than those in the control group （P〈0.05）. The positive expression rate of MMP-9 protein in the experimental and normal groups was significantly lower than that in the control group （P〈0.05）. No significant difference in the positive expression rates of the three proteins was detected between the experimental and normal groups （P〉0.05）. Conclusions Blockage of costimulatory signal CD86 at early pregnancy can treat uncertain recurrent spontaneous abortion by stimulating the expression of TGF-β1, MMP-9 and PAl-1 and reducing the embryo resorption rate.展开更多
文摘In the present study, the effect of blockage of the costimulatory signal CD86 at time of implantation on the expressions of TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins at the maternal-fetal interface and the outcome of pregnancy in mufine abortion-prone model was investigated, in which the CBA/J × DBA/2 matings were used as the abortion-prone model and the CBA/J × BALB/c matings used as the normal pregnant model. The study was performed in following three groups： 2 groups of the abortion-prone model, which were experimental group and control experimental group, and 1 group of normal pregnant model, and each group had 10 pregnant CBA/J mice exclusively. Female pregnant CBA/J mice in the experimental group received an intraperitoneal （i. p. ） injection of 100μg of antimouse CD86 mAb in 200 μl of PBS at day 4.5 of gestation, and the irrelevant-isotope matched rat IgG2b was administrated in the control experimental group with the same dosage and at same time. For the normal pregnant group, no treatment was given. The pregnant CBA/J mice were killed on day 13.5 of gestation. Then, the embryo resorption rate was calculated and the expressions of TGF-β1, MMP-9, TIMP3 and PAI-1 were detected by using immunohistochemical methods. It was demonstrated that the embryo resorption rate in the experimental group was significantly reduced in comparison with that in the control experimental group （X^2 = 7.441, P = 0.006）, but there was no significant difference with that in normal pregnant group （X^2 = 0.016, P = 0.898）. The expressions of TGF-β1 and PAI-1 in the experimental group were significantly increased in comparison with that in the control experimental group （P =0.010, P = 0.003, respectively）, with no significant difference from that in the nonnal pregnant group （P = 0.500）. However, the expression of MMP-9 in the experimental group was significantly reduced in comparison with that in the control experimental group （P = 0.012） with no significant difference from that in the normal pregnant group （P = 0.500）. The expression of TIMP-3 in the experimental group showed no significant difference both with the control experimental group （ P = 0. 328） and the normal pregnant group （ P = 0. 500）. It is concluded that the blockage of the costimulatory molecule CD86 at early stage of gestation can render TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins to express their immuno-tolerant effects through their characteristic pathways and induce the reduction of the embryo resorption rate in the natural abortion-prone model of mice to the level of normal pregnancy.
基金This work was supported by the grants from the Technology Department of National Population and Family Planning Commission of China (No. 2005 C1-41).
文摘Background Inhibition of the key costimulatory signals results in T cell anergy, indicating the alloantigen-specific immunologic unresponsiveness. In this study, the effect of blockage of costimulatory signal CD86 on murine abortion-prone model was studied. Methods Thirty CBA/J female mice cohabitated with DBA/2 male or BALB/c male mice were investigated. CBNJ xDBN2 matings were used as the abortion-prone model, and CBA/J × BALB/c matings were used as the normal pregnant model. The abortion-prone models were divided into experimental and control groups, and the normal pregnant models were set as a normal group （10 mice in each group）. The mice in the experimental group were treated with anti-mouse CD86 monoclonal antibody （mAb） （100 μg） on day 4.5 of gestation, while the controls received irrelevant-isotype matched rat IgG2b. As for the normal group, nothing was given to the mice. The mice were killed on day 13.5 of gestation, embryo resorption rate and the expression of transforming growth factor β1 （TGF-β1）, plasminogen activator inhibitor 1 （PAI-1）, and matrix metalloproteinase 9 （MMP-9） were detected. Then the data were analyzed by Chi-square test and Fisher＇s exact test. Results The embryo resorption rate in the experimental （8.2%） and normal groups （7.7%） was significantly lower than that of the control （23.5%, P〈0.05）. No significant difference was detected between the experimental and normal groups （P〉0.05）. The positive expression rates of TGF-β1 and PAl-1 proteins in the experimental and normal groups were significantly higher than those in the control group （P〈0.05）. The positive expression rate of MMP-9 protein in the experimental and normal groups was significantly lower than that in the control group （P〈0.05）. No significant difference in the positive expression rates of the three proteins was detected between the experimental and normal groups （P〉0.05）. Conclusions Blockage of costimulatory signal CD86 at early pregnancy can treat uncertain recurrent spontaneous abortion by stimulating the expression of TGF-β1, MMP-9 and PAl-1 and reducing the embryo resorption rate.
