Increasing evidence has revealed that maternal cytomegalovirus （CMV） infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related...Increasing evidence has revealed that maternal cytomegalovirus （CMV） infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation. Meanwhile, abnormal expression of Toll-like receptor 2 （TLR2） and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies. IL-6 and IL- 10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders. To investigate whether murine CMV （MCMV） infection causes alterations in placental IL-6/10 and TLR2/4 levels, we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection. Mouse model of acute MCMV infection during pregnancy was created, and pre-pregnant MCMV infected, lipopolysaccharide （LPS）-treated and uninfected mice were used as controls. At E13.5, E 14.5 and E 18.5, placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed. The results showed that after acute MCMV infection, the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5, accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights. However, LPS 50 ktg/kg could decrease the IL-6 expression at E13.5 and E14.5. This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more pro- inflammatory cytokine IL-6. High dose of LPS stimulation （50 gg/kg） during pregnancy can lead to down-regulation of IL-6 levels in the late stage. Imbalance of IL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.展开更多
In order to investigate the role of interleukin 4 in experimental murine systemic Candidiasis, we created the intact and dexamethasone induced immunosuppressed murine systemic Candidiasis models. In these models, t...In order to investigate the role of interleukin 4 in experimental murine systemic Candidiasis, we created the intact and dexamethasone induced immunosuppressed murine systemic Candidiasis models. In these models, two site ELISA and RT PCR were applied to determine the level of IL 4 protein and mRNA expression in spleens respectively, clone forming units of infected kidneys were determined with the plating dilution method, and mean survival time of the mice was recorded. The results showed that, when compared with the controls, protein level of IL 4 increased in both intact mice infected with lethal doses of yeast (day 3, P <0.05; day 7, P <0 001) and immunosuppressed mice infected with sublethal doses of yeast (day 3, P >0.05; day 7, P <0.05). Furthermore, the level of IL 4 was higher on day 7 than on day 3 after infection ( P <0 001 and P <0.05 respectively in two groups). The tendency of IL 4mRNA expression was similar with that of IL 4 protein. As for fungal loads in kidneys, CFUs were significantly higher on day 7 than on day 3 after infection . Mice in both groups succumbed to infection within several days. It was suggested that IL 4 might play a promoting role in the development of murine systemic Candidiasis.展开更多
Thymosin β4（Tβ4） is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells（m ESCs...Thymosin β4（Tβ4） is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells（m ESCs） proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on m ESCs. Target genes during m ESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the m ESCs-derived cardiomyocytes. It was found that Tβ4 decreased m ESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, m ESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these m ESCs. Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant ？-catenin. Under m ESCs differentiation, Tβ4 treatment did not change the expression of cardiovascular cell markers α-MHC, PECAM, and α-SMA. Neither the electrophysiological properties of m ESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4. In conclusion, Tβ4 suppressed m ESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tβ4 did not influence the in vitro cardiovascular differentiation.展开更多
文摘Increasing evidence has revealed that maternal cytomegalovirus （CMV） infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation. Meanwhile, abnormal expression of Toll-like receptor 2 （TLR2） and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies. IL-6 and IL- 10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders. To investigate whether murine CMV （MCMV） infection causes alterations in placental IL-6/10 and TLR2/4 levels, we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection. Mouse model of acute MCMV infection during pregnancy was created, and pre-pregnant MCMV infected, lipopolysaccharide （LPS）-treated and uninfected mice were used as controls. At E13.5, E 14.5 and E 18.5, placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed. The results showed that after acute MCMV infection, the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5, accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights. However, LPS 50 ktg/kg could decrease the IL-6 expression at E13.5 and E14.5. This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more pro- inflammatory cytokine IL-6. High dose of LPS stimulation （50 gg/kg） during pregnancy can lead to down-regulation of IL-6 levels in the late stage. Imbalance of IL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.
文摘In order to investigate the role of interleukin 4 in experimental murine systemic Candidiasis, we created the intact and dexamethasone induced immunosuppressed murine systemic Candidiasis models. In these models, two site ELISA and RT PCR were applied to determine the level of IL 4 protein and mRNA expression in spleens respectively, clone forming units of infected kidneys were determined with the plating dilution method, and mean survival time of the mice was recorded. The results showed that, when compared with the controls, protein level of IL 4 increased in both intact mice infected with lethal doses of yeast (day 3, P <0.05; day 7, P <0 001) and immunosuppressed mice infected with sublethal doses of yeast (day 3, P >0.05; day 7, P <0.05). Furthermore, the level of IL 4 was higher on day 7 than on day 3 after infection ( P <0 001 and P <0.05 respectively in two groups). The tendency of IL 4mRNA expression was similar with that of IL 4 protein. As for fungal loads in kidneys, CFUs were significantly higher on day 7 than on day 3 after infection . Mice in both groups succumbed to infection within several days. It was suggested that IL 4 might play a promoting role in the development of murine systemic Candidiasis.
基金supposed by grants from National Natural Science Foundation of China(No.81100818,No.31100828 and No.81070342)the Fundamental Research Funds for the Central Universities(HUST:No.2012TS036)
文摘Thymosin β4（Tβ4） is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells（m ESCs） proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on m ESCs. Target genes during m ESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the m ESCs-derived cardiomyocytes. It was found that Tβ4 decreased m ESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, m ESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these m ESCs. Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant ？-catenin. Under m ESCs differentiation, Tβ4 treatment did not change the expression of cardiovascular cell markers α-MHC, PECAM, and α-SMA. Neither the electrophysiological properties of m ESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4. In conclusion, Tβ4 suppressed m ESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tβ4 did not influence the in vitro cardiovascular differentiation.
