Pingyangmycin (bleomycin A5 hydrochloride,PYM) is one of the anti-neoplastic agents which have been commonly used to treat venous malformations.However,the underlying mechanism by which PYM treats venous malformations...Pingyangmycin (bleomycin A5 hydrochloride,PYM) is one of the anti-neoplastic agents which have been commonly used to treat venous malformations.However,the underlying mechanism by which PYM treats venous malformations remains poorly understood.It was reported that venous endothelial cells could recruit neutrophils via adhesion molecules (E-selectin,ICAM-1,ICAM-3,VCAM-1) during the acute/chronic inflammation and subsequent histological fibrosis after sclerotherapy with PYM.This study explored if the expression of E-selectin,ICAM-1,ICAM-3 and VCAM-1 in human venous malformation endothelial cells could be affected by PYM.HVMECs were cultured from human venous malformation tissue.Expressions of E-selectin,ICAM-1,ICAM-3 and VCAM-1 on HVMECs in response to PYM were analyzed by cell ELISA.The relative levels of mRNA expression in the cells were semi-quantified.The results showed that PYM up-regulated the expressions of E-selectin,ICAM-3,VCAM-1 and ICAM-1 in both time-and concentration-dependent manner.Our findings suggested that PYM could induce the expression of adhesion molecules in HVMECs,which might be a possible mechanism by which sclerotherapy by intralesional injection of PYM treats venous malformations.展开更多
Background： Dendritic cells （DCs） play an important role in host defense against pathogen infection. DC-specific intercellular adhesion moleeule-3-grabbing nonintegrin （SIGN） is a group II C-type lectin receptor ...Background： Dendritic cells （DCs） play an important role in host defense against pathogen infection. DC-specific intercellular adhesion moleeule-3-grabbing nonintegrin （SIGN） is a group II C-type lectin receptor and specifically expressed on the surface of DCs. This study aimed to determine whether DC-SIGN affects intracellular signaling activation, Th1/Th2 imbalance and aspergillus immune evasion in aspergillus infection, and explore the application of DC-SIGN-modified DCs in immunotherapy. Methods： DCs were first obtained from the mononuelear ceils of peripheral blood. The interferon （IFN）-γand dexamethasone （Dex） were used to stimulate DCs. The expression ofDC-SIGN, Th 1 and Th2 cytokines, and the capacity of DCs in stimulating T cells proliferation and phagocytosis, and nuclear factor （NF）-κB activation were analyzed. In addition, adenovirus expression vector Ad-DC-SIGN was generated to transfect DCs. Mannan was used to block DC-SIGN signaling for confirming the involvement of DC-SIGN function in Aspergillus fumigatus （Af）-induced DCs maturation. The unpaired, two-tailed Student＇s t-test was used in the comparisons between two groups. Results： Exogenous IFN-y could activate Af-induced DCs and promote the Th0 cells toward Th 1 profile （interleukin [IL]- 12 in I FN-y/Af group： 50.96 ± 4.38 pg/ml; control/Afgroup： 29.70 ±2.00 pg/ml, t = 10.815, P 〈 0.001 ）. On the other hand, Dex inhibited the secretion of Th2 cytokines （IL- 10 in Dex/Af group： 5.27 ± 0.85 pg/ml; control/Af group： 15.14 ± 1.40 pg/ml, t = 14.761, P 〈 0.001 ））, and successfully caused immunosuppression. Alier transfection with Ad-DC-SIGN, DCs have improved phagocytosis （phagocytosis rates in Ad-DC-SIGN group： 74.0% ± 3.4%; control group： 64.7% ± 6.8%, t = 3.104, P = 0.013）. There was more Thl cytokine secreted in the Af-induced DC-SIGN modified DCs （IL-12 in Ad-DC-SIGN/Af group： 471.98 ± 166.31 pg/ml; control/Af group： 33.35 ± 5.98 pg/ml, t = 6.456, P = 0.001 ）, correl展开更多
Background： The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin （DC-SIGN） in renal tubular epithelial cells has been thought to be highly correlated with the occurrence ...Background： The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin （DC-SIGN） in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock （HS） is unknown. The present study airned to investigate this phenomenon and the inhibitory effect of Vitamin C （VitC）. Methods： A Sprague Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-or and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times （2-24 h） alter HS （six rats in each group）, with or without VitC treatment belbre resuscitation, were evaluated. Results： HS induced DC-SIGN expression in rat tubular epithelial cells. The proinflarnmatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenornena induced by HS were relieved when the rats were treated with VitC before resuscitation. Conclusions： The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflarnmatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.展开更多
基金supported by the Natural Science Foundation of Hubei province,China (No.2010CDB07907)
文摘Pingyangmycin (bleomycin A5 hydrochloride,PYM) is one of the anti-neoplastic agents which have been commonly used to treat venous malformations.However,the underlying mechanism by which PYM treats venous malformations remains poorly understood.It was reported that venous endothelial cells could recruit neutrophils via adhesion molecules (E-selectin,ICAM-1,ICAM-3,VCAM-1) during the acute/chronic inflammation and subsequent histological fibrosis after sclerotherapy with PYM.This study explored if the expression of E-selectin,ICAM-1,ICAM-3 and VCAM-1 in human venous malformation endothelial cells could be affected by PYM.HVMECs were cultured from human venous malformation tissue.Expressions of E-selectin,ICAM-1,ICAM-3 and VCAM-1 on HVMECs in response to PYM were analyzed by cell ELISA.The relative levels of mRNA expression in the cells were semi-quantified.The results showed that PYM up-regulated the expressions of E-selectin,ICAM-3,VCAM-1 and ICAM-1 in both time-and concentration-dependent manner.Our findings suggested that PYM could induce the expression of adhesion molecules in HVMECs,which might be a possible mechanism by which sclerotherapy by intralesional injection of PYM treats venous malformations.
基金The study was supported by a grant from the National Natural Science Foundation of China （No. 30772019）.
文摘Background： Dendritic cells （DCs） play an important role in host defense against pathogen infection. DC-specific intercellular adhesion moleeule-3-grabbing nonintegrin （SIGN） is a group II C-type lectin receptor and specifically expressed on the surface of DCs. This study aimed to determine whether DC-SIGN affects intracellular signaling activation, Th1/Th2 imbalance and aspergillus immune evasion in aspergillus infection, and explore the application of DC-SIGN-modified DCs in immunotherapy. Methods： DCs were first obtained from the mononuelear ceils of peripheral blood. The interferon （IFN）-γand dexamethasone （Dex） were used to stimulate DCs. The expression ofDC-SIGN, Th 1 and Th2 cytokines, and the capacity of DCs in stimulating T cells proliferation and phagocytosis, and nuclear factor （NF）-κB activation were analyzed. In addition, adenovirus expression vector Ad-DC-SIGN was generated to transfect DCs. Mannan was used to block DC-SIGN signaling for confirming the involvement of DC-SIGN function in Aspergillus fumigatus （Af）-induced DCs maturation. The unpaired, two-tailed Student＇s t-test was used in the comparisons between two groups. Results： Exogenous IFN-y could activate Af-induced DCs and promote the Th0 cells toward Th 1 profile （interleukin [IL]- 12 in I FN-y/Af group： 50.96 ± 4.38 pg/ml; control/Afgroup： 29.70 ±2.00 pg/ml, t = 10.815, P 〈 0.001 ）. On the other hand, Dex inhibited the secretion of Th2 cytokines （IL- 10 in Dex/Af group： 5.27 ± 0.85 pg/ml; control/Af group： 15.14 ± 1.40 pg/ml, t = 14.761, P 〈 0.001 ））, and successfully caused immunosuppression. Alier transfection with Ad-DC-SIGN, DCs have improved phagocytosis （phagocytosis rates in Ad-DC-SIGN group： 74.0% ± 3.4%; control group： 64.7% ± 6.8%, t = 3.104, P = 0.013）. There was more Thl cytokine secreted in the Af-induced DC-SIGN modified DCs （IL-12 in Ad-DC-SIGN/Af group： 471.98 ± 166.31 pg/ml; control/Af group： 33.35 ± 5.98 pg/ml, t = 6.456, P = 0.001 ）, correl
文摘Background： The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin （DC-SIGN） in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock （HS） is unknown. The present study airned to investigate this phenomenon and the inhibitory effect of Vitamin C （VitC）. Methods： A Sprague Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-or and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times （2-24 h） alter HS （six rats in each group）, with or without VitC treatment belbre resuscitation, were evaluated. Results： HS induced DC-SIGN expression in rat tubular epithelial cells. The proinflarnmatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenornena induced by HS were relieved when the rats were treated with VitC before resuscitation. Conclusions： The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflarnmatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.
